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Wikipedia

Dysferlin

January 01, 1970

Dysferlin also known as dystrophy-associated fer-1-like protein is a protein that in humans is encoded by the DYSF gene.[5] Dysferlin is linked with plasma membrane repair.,[6] stabilization of calcium signaling[7][8][9] and the development of the T-tubule system of the muscle[10] A defect in the DYSF gene, located on chromosome 2p12-14, results in several types of muscular dystrophy; including Miyoshi myopathy (MM), Limb-girdle muscular dystrophy type 2B (LGMD2B) and Distal Myopathy (DM). A reduction or absence of dysferlin, termed dysferlinopathy, usually becomes apparent in the third or fourth decade of life and is characterised by weakness and wasting of various voluntary skeletal muscles.[11] Pathogenic mutations leading to dysferlinopathy can occur throughout the DYSF gene.

DYSF
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesDYSF, FER1L1, LGMD2B, MMD1, dysferlin, LGMDR2
External IDsOMIM: 603009; MGI: 1349385; HomoloGene: 20748; GeneCards: DYSF; OMA:DYSF - orthologs
Orthologs
SpeciesHumanMouse
Entrez

8291

26903

Ensembl

ENSG00000135636

ENSMUSG00000033788

UniProt

O75923

Q9ESD7

RefSeq (mRNA)

NM_001077694
NM_021469
NM_001310152

RefSeq (protein)
Location (UCSC)Chr 2: 71.45 – 71.69 MbChr 6: 83.99 – 84.19 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Structure edit

Ferlin family
Identifiers
SymbolDysferlin
OPM superfamily452
OPM protein4cah
Membranome205

The human dysferlin protein is a 237 kilodalton type-II transmembrane protein.[12][13][14][15][16] It contains a large intracellular cytoplasmic N-terminal domain, an extreme C-terminal transmembrane domain, and a short C-terminal extracellular domain. The cytosolic domain of dysferlin is composed of seven highly conserved C2 domains (C2A-G) which are conserved across several proteins within the ferlin family, including dysferlin homolog myoferlin.[17][18][13] In fact, the C2 domain at any given position is more similar to the C2 domain at the corresponding position within other ferlin family members than the adjacent C2 domain within the same protein. This suggests that each individual C2 domain may in fact play a specific role in dysferlin function and each has in fact been shown to be required for two of dysferlin's roles stabilization of calcium signaling and membrane repair.[19] Mutations in each of these domains can cause dysferlinopathy. A crystal structure of the C2A domain of human dysferlin has been solved, and reveals that the C2A domain changes conformation when interacting with calcium ions,[13] which is consistent with a growing body of evidence suggesting that the C2A domain plays a role in calcium-dependent lipid binding.[20] Its ability to stabilize calcium signaling in the intact dysferlin protein depends on its calcium binding activity.[21] In addition to the C2 domains, dysferlin also contains "FerA" and "DysF" domains. Mutations in both FerA[22] and DysF[23] can cause muscular dystrophies. DysF domain has an interesting structure as in contains one DysF domain within another DysF domain, a result of gene duplication; however, the function of this domain is currently unknown.[23] FerA domain is conserved among all members of ferlin protein family. FerA domain is a four helix bundle and it can interact with membrane, usually in a calcium-dependent manner.[22]

Function edit

The most intensively studied role for dysferlin is in a cellular process called membrane repair. Membrane repair is a critical mechanism by which cells are able to seal dramatic wounds to the plasma membrane. Muscle is thought to be particularly prone to membrane wounds given that muscle cells transmit high force and undergo cycles of contraction. Dysferlin is highly expressed in muscle, and is homologous to the ferlin family of proteins, which are thought to regulate membrane fusion across a wide variety of species and cell types.[24] Several lines of evidence suggest that dysferlin may be involved in membrane repair in muscle. First, dysferlin-deficient muscle fibers show accumulation of vesicles (which are critical for membrane repair in non-muscle cell types) near membrane lesions, indicating that dysferlin may be required for fusion of repair vesicles with the plasma membrane. Further, dysferlin-deficient muscle fibers take up extracellular dyes to a greater extent than wild-type muscle fibers following laser-induced wounding in-vitro.[25] Dysferlin is also markedly enriched at membrane lesions with several additional proteins thought to be involved in membrane resealing, including annexin and MG53.[26] Exactly how dysferlin contributes to membrane resealing is not clear, but biochemical evidence indicates that dysferlin may bind lipids in a calcium-dependent manner, consistent with a role for dysferlin in regulating fusion of repair vesicles with the sarcolemma during membrane repair.[27] Furthermore, live-cell imaging of dysferlin-eGFP expressing myotubes indicates that dysferlin localizes to a cellular compartment that responds to injury by forming large dysferlin-containing vesicles, and formation of these vesicles may contribute to wound repair.[28] Dysferlin may also be involved in Alzheimer's disease pathogenesis.[29]

Another well studied role for dysferlin is in stabilization of calcium signaling, especially following a mild injury. This approach was based on two observations: that muscle lacking dysferlin that is injured by eccentric contractions can repair its plasma membrane, or sarcolemma, as efficiently as healthy muscle can,[30] and that most of the dysferlin in healthy muscle is concentrated in the transverse tubules at triad junctions,[31][32] where calcium release is regulated. Destabilization of signaling in dysferlinopathic muscle can result in the generation of calcium waves,[33] which can contribute to the disease pathology. Nearly every change in dysferlin that affects membrane repair also destabilizes calcium signaling,[34] suggesting that these two activities are closely linked. Remarkably, however, membrane repair requires calcium ions, whereas calcium ions contribute to the destabilization of signaling when dysferlin is absent or mutated.[35] These paradoxical results have yet to be reconciled.

Interactions edit

Dysferlin has been shown to bind to itself, to form dimers and perhaps larger oligomers.[36] It can also has been shown to interact with Caveolin 3 in skeletal muscle,[37] and this interaction is thought to retain dysferlin within the plasma membrane.[38] Dysferlin also interacts with MG53, and a functional interaction between dysferlin, caveolin-3 and MG53 is thought to be critical for membrane repair in skeletal muscle.[39]

References edit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000135636 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000033788 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Passos-Bueno MR, Richard I, Vainzof M, Fougerousse F, Weissenbach J, Broux O, Cohen D, Akiyama J, Marie SK, Carvalho AA (May 1993). "Evidence of genetic heterogeneity in the autosomal recessive adult forms of limb-girdle muscular dystrophy following linkage analysis with 15q probes in Brazilian families". Journal of Medical Genetics. 30 (5): 385–7. doi:10.1136/jmg.30.5.385. PMC 1016373. PMID 8320700.
  6. ^ "Entrez Gene: DYSF dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive)".
  7. ^ Kerr JP, Ziman AP, Mueller AL, et al. (December 2013). "Dysferlin Stabilizes Stress-induced Ca2+ Signaling in the Transverse Tubule Membrane". Proc. Natl. Acad. Sci. USA. 110 (51): 20831–20836. Bibcode:2013PNAS..11020831K. doi:10.1073/pnas.1307960110. PMC 3870721. PMID 24302765.
  8. ^ Kerr JP, Ward CW, Bloch RJ (March 2014). "Dysferlin at Transverse Tubules Regulates Ca2+ Homeostasis in Skeletal Muscle". Frontiers in Physiology. 5: 89. doi:10.3389/fphys.2014.00089. PMC 3944681. PMID 24639655.
  9. ^ Lukyanenko V, Muriel JM, Bloch RJ (August 2017). "Coupling of Excitation to Ca2+ Release is Modulated by Dysferlin". J. Physiol. 595 (15): 5191–5207. doi:10.1113/JP274515. PMC 5538227. PMID 8568606.
  10. ^ Hofhuis J, Bersch K, Wagner S, Molina C, Fakuade FE, Iyer LM, Streckfuss-Bömeke K, Toischer K, Zelarayán LC, Voigt N, Nikolaev VO, Maier LS, Klinge L, Thoms S (July 2020). "Dysferlin links excitation-contraction coupling to structure and maintenance of the cardiac transverse-axial tubule system". Europace. 22 (7): 1119–1131. doi:10.1093/europace/euaa093. PMID 32572487.
  11. ^ Leiden University Medical Center, Center for Human and Clinical Genetics - Dysferlin Retrieved 21 June 2007.
  12. ^ Kawahara G, Serafini PR, Myers JA, Alexander MS, Kunkel LM (September 2011). "Characterization of zebrafish dysferlin by morpholino knockdown". Biochemical and Biophysical Research Communications. 413 (2): 358–363. doi:10.1016/j.bbrc.2011.08.105. PMC 4526276. PMID 21893049.
  13. ^ a b c Fuson K, Rice A, Mahling R, Snow A, Nayak K, Shanbhogue P, et al. (January 2014). "Alternate splicing of dysferlin C2A confers Ca²⁺-dependent and Ca²⁺-independent binding for membrane repair". Structure. 22 (1): 104–115. doi:10.1016/j.str.2013.10.001. PMC 5993433. PMID 24239457.
  14. ^ Demonbreun AR, Allen MV, Warner JL, Barefield DY, Krishnan S, Swanson KE, et al. (June 2016). "Enhanced Muscular Dystrophy from Loss of Dysferlin Is Accompanied by Impaired Annexin A6 Translocation after Sarcolemmal Disruption". The American Journal of Pathology. 186 (6): 1610–1622. doi:10.1016/j.ajpath.2016.02.005. PMC 4901136. PMID 27070822.
  15. ^ Cacciottolo M, Numitone G, Aurino S, Caserta IR, Fanin M, Politano L, et al. (September 2011). "Muscular dystrophy with marked Dysferlin deficiency is consistently caused by primary dysferlin gene mutations". European Journal of Human Genetics. 19 (9): 974–980. doi:10.1038/ejhg.2011.70. PMC 3179367. PMID 21522182.
  16. ^ Matsuda C, Kiyosue K, Nishino I, Goto Y, Hayashi YK (October 2015). "Dysferlinopathy Fibroblasts Are Defective in Plasma Membrane Repair". PLOS Currents. 7. doi:10.1371/currents.md.5865add2d766f39a0e0411d38a7ba09c. PMC 4639325. PMID 26579332.
  17. ^ Vafiadaki E, Reis A, Keers S, Harrison R, Anderson LV, Raffelsberger T, et al. (March 2001). "Cloning of the mouse dysferlin gene and genomic characterization of the SJL-Dysf mutation". NeuroReport. 12 (3): 625–629. doi:10.1097/00001756-200103050-00039. PMID 11234777. S2CID 22800606.
  18. ^ Abdullah N, Padmanarayana M, Marty NJ, Johnson CP (January 2014). "Quantitation of the calcium and membrane binding properties of the C2 domains of dysferlin". Biophysical Journal. 106 (2): 382–389. Bibcode:2014BpJ...106..382A. doi:10.1016/j.bpj.2013.11.4492. PMC 3907215. PMID 24461013.
  19. ^ Muriel J, Lukyanenko V, Kwiatkowski T, Bhattacharya S, Garman D, Weisleder N, Bloch RJ (April 2022). "The C2 domains of dysferlin: roles in membrane localization, Ca2+ signalling and sarcolemmal repair". The Journal of Physiology. 600 (8): 1953–1968. doi:10.1113/JP282648. PMC 9285653. PMID 35156706.
  20. ^ Therrien C, Di Fulvio S, Pickles S, Sinnreich M (March 2009). "Characterization of lipid binding specificities of dysferlin C2 domains reveals novel interactions with phosphoinositides". Biochemistry. 48 (11): 2377–2384. doi:10.1021/bi802242r. PMID 19253956.
  21. ^ Lukyanenko V, Muriel J, Garman D, Breydo L, Bloch RJ (November 2022). "Elevated Ca2+ at the triad junction underlies dysregulation of Ca2+ signaling in dysferlin-null skeletal muscle". Frontiers in Physiology. 13: 1032447. doi:10.3389/fphys.2022.1032447. PMC 9669649. PMID 36406982.
  22. ^ a b Harsini FM, Chebrolu S, Fuson KL, White MA, Rice AM, Sutton RB (July 2018). "FerA is a Membrane-Associating Four-Helix Bundle Domain in the Ferlin Family of Membrane-Fusion Proteins". Scientific Reports. 8 (1): 10949. Bibcode:2018NatSR...810949H. doi:10.1038/s41598-018-29184-1. PMC 6053371. PMID 30026467.
  23. ^ a b Sula A, Cole AR, Yeats C, Orengo C, Keep NH (January 2014). "Crystal structures of the human Dysferlin inner DysF domain". BMC Structural Biology. 14: 3. doi:10.1186/1472-6807-14-3. PMC 3898210. PMID 24438169.
  24. ^ Bashir R, Britton S, Strachan T, Keers S, Vafiadaki E, Lako M, Richard I, Marchand S, Bourg N, Argov Z, Sadeh M, Mahjneh I, Marconi G, Passos-Bueno MR, Moreira Ede S, Zatz M, Beckmann JS, Bushby K (1998). "A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B". Nat. Genet. 20 (1): 37–42. doi:10.1038/1689. PMID 9731527. S2CID 24234676.
  25. ^ Bansal D, Miyake K, Vogel SS, Groh S, Chen CC, Williamson R, McNeil PL, Campbell KP (2003). "Defective membrane repair in dysferlin-deficient muscular dystrophy". Nature. 423 (6936): 168–72. Bibcode:2003Natur.423..168B. doi:10.1038/nature01573. PMID 12736685. S2CID 4402938.
  26. ^ Roostalu U, Strähle U (2012). "In vivo imaging of molecular interactions at damaged sarcolemma". Dev. Cell. 22 (3): 515–29. doi:10.1016/j.devcel.2011.12.008. PMID 22421042.
  27. ^ Abdullah N, Padmanarayana M, Marty NJ, Johnson CP (2014). "Quantitation of the calcium and membrane binding properties of the C2 domains of dysferlin". Biophys. J. 106 (2): 382–9. Bibcode:2014BpJ...106..382A. doi:10.1016/j.bpj.2013.11.4492. PMC 3907215. PMID 24461013.
  28. ^ McDade JR, Michele DE (2014). "Membrane damage-induced vesicle-vesicle fusion of dysferlin-containing vesicles in muscle cells requires microtubules and kinesin". Hum. Mol. Genet. 23 (7): 1677–86. doi:10.1093/hmg/ddt557. PMC 3943514. PMID 24203699.
  29. ^ Chen JA, Wang Q, Davis-Turak J, et al. (April 2015). "A multiancestral genome-wide exome array study of Alzheimer disease, frontotemporal dementia, and progressive supranuclear palsy". JAMA Neurology. 72 (4): 414–22. doi:10.1001/jamaneurol.2014.4040. PMC 4397175. PMID 25706306.
  30. ^ Roche JA, Lovering RM, Vanapalli R, et al. (Feb 2010). "Extensive Mononuclear Infiltration and Myogenesis Characterize the Recovery of Dysferlin-Null Skeletal Muscle from Contraction-Induced Injuries". Am. J. Physiol. Cell Physiol. 298 (2): C298–C312. doi:10.1152/ajpcell.00122.2009. PMC 2822489. PMID 9923419.
  31. ^ Kerr JP, Ziman AP, Mueller AL, et al. (December 2013). "Dysferlin Stabilizes Stress-induced Ca2+ Signaling in the Transverse Tubule Membrane". Proc. Natl. Acad. Sci. USA. 110 (51): 20831–20836. Bibcode:2013PNAS..11020831K. doi:10.1073/pnas.1307960110. PMC 3870721. PMID 24302765.
  32. ^ Roche JA, Lovering RM, Vanapalli R, et al. (Feb 2010). "Extensive Mononuclear Infiltration and Myogenesis Characterize the Recovery of Dysferlin-Null Skeletal Muscle from Contraction-Induced Injuries". Am. J. Physiol. Cell Physiol. 298 (2): C298–C312. doi:10.1152/ajpcell.00122.2009. PMC 2822489. PMID 9923419.
  33. ^ Lukyanenko V, Muriel J, Bloch RJ (August 2017). "Coupling of Excitation to Ca2+ Release is Modulated by Dysferlin". J. Physiol. 595 (15): 5191–5207. doi:10.1113/JP274515. PMC 5538227. PMID 8568606.
  34. ^ Muriel J, Lukyanenko V, Kwiatkowski T, et al. (Apr 2022). "The C2 Domains of Dysferlin: Roles in Membrane Localization, Stabilization of Ca2+ Signaling, and Membrane Repair". J. Physiol. 600 (8): 1953–1968. doi:10.1113/JP282648. PMC 9285653. PMID 35156706.
  35. ^ Muriel J, Lukyanenko V, Kwiatkowski T, et al. (Apr 2022). "The C2 Domains of Dysferlin: Roles in Membrane Localization, Stabilization of Ca2+ Signaling, and Membrane Repair". J. Physiol. 600 (8): 1953–1968. doi:10.1113/JP282648. PMC 9285653. PMID 35156706.
  36. ^ Roche JA, Ru L, ONeill A, et al. (Nov 2011). "Unmasking intracellular dysferlin". J. Histochem. 59 (11): 964–975. doi:10.1369/0022155411423274. PMC 3261626. PMID 22043020.
  37. ^ Matsuda C, Hayashi YK, Ogawa M, Aoki M, Murayama K, Nishino I, Nonaka I, Arahata K, Brown RH (August 2001). "The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal muscle". Hum. Mol. Genet. 10 (17): 1761–6. doi:10.1093/hmg/10.17.1761. PMID 11532985.
  38. ^ Hernández-Deviez DJ, Howes MT, Laval SH, Bushby K, Hancock JF, Parton RG (2008). "Caveolin regulates endocytosis of the muscle repair protein, dysferlin" (PDF). J. Biol. Chem. 283 (10): 6476–88. doi:10.1074/jbc.M708776200. PMID 18096699. S2CID 8337318.
  39. ^ Cai C, Weisleder N, Ko JK, Komazaki S, Sunada Y, Nishi M, Takeshima H, Ma J (2009). "Membrane repair defects in muscular dystrophy are linked to altered interaction between MG53, caveolin-3, and dysferlin". J. Biol. Chem. 284 (23): 15894–902. doi:10.1074/jbc.M109.009589. PMC 2708885. PMID 19380584.

Further reading edit

  • Bejaoui K, Hirabayashi K, Hentati F, Haines JL, Ben Hamida C, Belal S, Miller RG, McKenna-Yasek D, Weissenbach J, Rowland LP (1995). "Linkage of Miyoshi myopathy (distal autosomal recessive muscular dystrophy) locus to chromosome 2p12-14". Neurology. 45 (4): 768–72. doi:10.1212/wnl.45.4.768. PMID 7723968. S2CID 31029040.
  • Bashir R, Strachan T, Keers S, Stephenson A, Mahjneh I, Marconi G, Nashef L, Bushby KM (1994). "A gene for autosomal recessive limb-girdle muscular dystrophy maps to chromosome 2p". Hum. Mol. Genet. 3 (3): 455–7. doi:10.1093/hmg/3.3.455. PMID 8012357.
  • Liu J, Aoki M, Illa I, Wu C, Fardeau M, Angelini C, Serrano C, Urtizberea JA, Hentati F, Hamida MB, Bohlega S, Culper EJ, Amato AA, Bossie K, Oeltjen J, Bejaoui K, McKenna-Yasek D, Hosler BA, Schurr E, Arahata K, de Jong PJ, Brown RH (1998). "Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy". Nat. Genet. 20 (1): 31–6. doi:10.1038/1682. PMID 9731526. S2CID 12018395.
  • Bashir R, Britton S, Strachan T, Keers S, Vafiadaki E, Lako M, Richard I, Marchand S, Bourg N, Argov Z, Sadeh M, Mahjneh I, Marconi G, Passos-Bueno MR, Moreira Ede S, Zatz M, Beckmann JS, Bushby K (1998). "A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B". Nat. Genet. 20 (1): 37–42. doi:10.1038/1689. PMID 9731527. S2CID 24234676.
  • Anderson LV, Davison K, Moss JA, Young C, Cullen MJ, Walsh J, Johnson MA, Bashir R, Britton S, Keers S, Argov Z, Mahjneh I, Fougerousse F, Beckmann JS, Bushby KM (1999). "Dysferlin is a plasma membrane protein and is expressed early in human development". Hum. Mol. Genet. 8 (5): 855–61. doi:10.1093/hmg/8.5.855. PMID 10196375.
  • Weiler T, Bashir R, Anderson LV, Davison K, Moss JA, Britton S, Nylen E, Keers S, Vafiadaki E, Greenberg CR, Bushby CR, Wrogemann K (1999). "Identical mutation in patients with limb girdle muscular dystrophy type 2B or Miyoshi myopathy suggests a role for modifier gene(s)". Hum. Mol. Genet. 8 (5): 871–7. doi:10.1093/hmg/8.5.871. PMID 10196377.
  • Matsuda C, Aoki M, Hayashi YK, Ho MF, Arahata K, Brown RH (1999). "Dysferlin is a surface membrane-associated protein that is absent in Miyoshi myopathy". Neurology. 53 (5): 1119–22. doi:10.1212/wnl.53.5.1119. PMID 10496277. S2CID 6068681.
  • Illa I, Serrano-Munuera C, Gallardo E, Lasa A, Rojas-García R, Palmer J, Gallano P, Baiget M, Matsuda C, Brown RH (2001). "Distal anterior compartment myopathy: a dysferlin mutation causing a new muscular dystrophy phenotype". Ann. Neurol. 49 (1): 130–4. doi:10.1002/1531-8249(200101)49:1<130::AID-ANA22>3.0.CO;2-0. PMID 11198284. S2CID 9278818.
  • Aoki M, Liu J, Richard I, Bashir R, Britton S, Keers SM, Oeltjen J, Brown HE, Marchand S, Bourg N, Beley C, McKenna-Yasek D, Arahata K, Bohlega S, Cupler E, Illa I, Majneh I, Barohn RJ, Urtizberea JA, Fardeau M, Amato A, Angelini C, Bushby K, Beckmann JS, Brown RH (2001). "Genomic organization of the dysferlin gene and novel mutations in Miyoshi myopathy". Neurology. 57 (2): 271–8. doi:10.1212/wnl.57.2.271. PMID 11468312. S2CID 31959549.
  • Matsuda C, Hayashi YK, Ogawa M, Aoki M, Murayama K, Nishino I, Nonaka I, Arahata K, Brown RH (2001). "The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal muscle". Hum. Mol. Genet. 10 (17): 1761–6. doi:10.1093/hmg/10.17.1761. PMID 11532985.
  • Ikezoe K, Furuya H, Ohyagi Y, Osoegawa M, Nishino I, Nonaka I, Kira J (2003). "Dysferlin expression in tubular aggregates: their possible relationship to endoplasmic reticulum stress". Acta Neuropathol. 105 (6): 603–9. doi:10.1007/s00401-003-0686-1. PMID 12664320. S2CID 7734282.
  • von Tell D, Bruder CE, Anderson LV, Anvret M, Ahlberg G (2003). "Refined mapping of the Welander distal myopathy region on chromosome 2p13 positions the new candidate region telomeric of the DYSF locus". Neurogenetics. 4 (4): 173–7. doi:10.1007/s10048-003-0154-z. PMID 12836053. S2CID 27539044.
  • Lennon NJ, Kho A, Bacskai BJ, Perlmutter SL, Hyman BT, Brown RH (2003). "Dysferlin interacts with annexins A1 and A2 and mediates sarcolemmal wound-healing". J. Biol. Chem. 278 (50): 50466–73. doi:10.1074/jbc.M307247200. PMID 14506282.
  • Katz JS, Rando TA, Barohn RJ, Saperstein DS, Jackson CE, Wicklund M, Amato AA (2003). "Late-onset distal muscular dystrophy affecting the posterior calves". Muscle Nerve. 28 (4): 443–8. doi:10.1002/mus.10458. PMID 14506716. S2CID 29825709.
  • Confalonieri P, Oliva L, Andreetta F, Lorenzoni R, Dassi P, Mariani E, Morandi L, Mora M, Cornelio F, Mantegazza R (2003). "Muscle inflammation and MHC class I up-regulation in muscular dystrophy with lack of dysferlin: an immunopathological study". J. Neuroimmunol. 142 (1–2): 130–6. doi:10.1016/S0165-5728(03)00255-8. PMID 14512171. S2CID 37727809.
  • Foxton RM, Laval SH, Bushby KM (2004). "Characterisation of the dysferlin skeletal muscle promoter". Eur. J. Hum. Genet. 12 (2): 127–31. doi:10.1038/sj.ejhg.5201092. PMID 14560310.
  • Cagliani R, Fortunato F, Giorda R, Rodolico C, Bonaglia MC, Sironi M, D'Angelo MG, Prelle A, Locatelli F, Toscano A, Bresolin N, Comi GP (2003). "Molecular analysis of LGMD-2B and MM patients: identification of novel DYSF mutations and possible founder effect in the Italian population". Neuromuscul. Disord. 13 (10): 788–95. doi:10.1016/S0960-8966(03)00133-0. PMID 14678801. S2CID 23179310.
  • Capanni C, Sabatelli P, Mattioli E, Ognibene A, Columbaro M, Lattanzi G, Merlini L, Minetti C, Maraldi NM, Squarzoni S (2003). "Dysferlin in a hyperCKaemic patient with caveolin 3 mutation and in C2C12 cells after p38 MAP kinase inhibition". Exp. Mol. Med. 35 (6): 538–44. doi:10.1038/emm.2003.70. PMID 14749532.
  • Brüss M, Homann J, Molderings GJ (2004). "[Dysferlinopathy as an extrahepatic cause for the elevation of serum transaminases]". Med. Klin. (Munich). 99 (6): 326–9. doi:10.1007/s00063-004-1046-1. PMID 15221058. S2CID 30657667.
  • Huang Y, de Morrée A, van Remoortere A, Bushby K, Frants RR, den Dunnen JT, van der Maarel SM (2008). "Calpain 3 is a modulator of the dysferlin protein complex in skeletal muscle". Hum. Mol. Genet. 17 (12): 1855–66. doi:10.1093/hmg/ddn081. PMC 2900895. PMID 18334579.

External links edit

  • GeneReviews/NCBI/NIH/UW entry on Dysferlinopathy including Miyoshi Distal Myopathy (Miyoshi Myopathy), Limb-Girdle Muscular Dystrophy Type 2B (LGMD2B)
  • LOVD mutation database: DYSF

January 01, 1970
dysferlin, also, known, dystrophy, associated, like, protein, protein, that, humans, encoded, dysf, gene, linked, with, plasma, membrane, repair, stabilization, calcium, signaling, development, tubule, system, muscle, defect, dysf, gene, located, chromosome, 2. Dysferlin also known as dystrophy associated fer 1 like protein is a protein that in humans is encoded by the DYSF gene 5 Dysferlin is linked with plasma membrane repair 6 stabilization of calcium signaling 7 8 9 and the development of the T tubule system of the muscle 10 A defect in the DYSF gene located on chromosome 2p12 14 results in several types of muscular dystrophy including Miyoshi myopathy MM Limb girdle muscular dystrophy type 2B LGMD2B and Distal Myopathy DM A reduction or absence of dysferlin termed dysferlinopathy usually becomes apparent in the third or fourth decade of life and is characterised by weakness and wasting of various voluntary skeletal muscles 11 Pathogenic mutations leading to dysferlinopathy can occur throughout the DYSF gene DYSFAvailable structuresPDBOrtholog search PDBe RCSBList of PDB id codes4CAH 4CAI 4IHB 4IQHIdentifiersAliasesDYSF FER1L1 LGMD2B MMD1 dysferlin LGMDR2External IDsOMIM 603009 MGI 1349385 HomoloGene 20748 GeneCards DYSF OMA DYSF orthologsGene location Human Chr Chromosome 2 human 1 Band2p13 2Start71 453 561 bp 1 End71 686 763 bp 1 Gene location Mouse Chr Chromosome 6 mouse 2 Band6 C3 6 36 14 cMStart83 985 572 bp 2 End84 188 042 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inbloodtriceps brachii musclevastus lateralis muscleexternal globus pallidusgastrocnemius muscledeltoid musclespleenright ventricletibialis anterior muscleleft ventricleTop expressed insoleus muscleskeletal muscle tissueinterventricular septumyolk sactriceps brachii muscletemporal musclequadriceps femoris muscledigastric musclemyocardium of ventriclegastrocnemius muscleMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functioncalcium ion binding metal ion binding protein binding calcium dependent phospholipid binding phospholipid binding lipid binding microtubule binding alpha tubulin bindingCellular componentintegral component of membrane endosome late endosome membrane T tubule plasma membrane endocytic vesicle early endosome sarcolemma extracellular exosome cytoplasmic vesicle membrane cytoplasmic vesicle lamellipodium microtubule organizing center nucleus Golgi apparatus microtubule membrane microdomainBiological processmuscle contraction plasma membrane repair vesicle fusion angiogenesis positive regulation of endothelial cell proliferation monocyte activation involved in immune response macrophage activation involved in immune response glycerol metabolic process negative regulation of gene expression lipid storage T tubule organization negative regulation of protein catabolic process skeletal muscle tissue regeneration fat cell differentiation positive regulation of cell adhesion negative regulation of phagocytosis cellular response to osmotic stress positive regulation of neutrophil chemotaxis regulation of calcium ion import negative regulation of high voltage gated calcium channel activity negative regulation of protein polyubiquitinationSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez829126903EnsemblENSG00000135636ENSMUSG00000033788UniProtO75923Q9ESD7RefSeq mRNA NM 001130455NM 001130976NM 001130977NM 001130978NM 001130979NM 001130980NM 001130981NM 001130982NM 001130983NM 001130984NM 001130985NM 001130986NM 001130987NM 003494NM 001077694NM 021469NM 001310152RefSeq protein NP 001123927NP 001124448NP 001124449NP 001124450NP 001124451NP 001124452NP 001124453NP 001124454NP 001124455NP 001124456NP 001124457NP 001124458NP 001124459NP 003485NP 001071162NP 001297081NP 067444NP 001390584NP 001390585NP 001390586NP 001390587Location UCSC Chr 2 71 45 71 69 MbChr 6 83 99 84 19 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Structure 2 Function 3 Interactions 4 References 5 Further reading 6 External linksStructure editFerlin familyIdentifiersSymbolDysferlinOPM superfamily452OPM protein4cahMembranome205 The human dysferlin protein is a 237 kilodalton type II transmembrane protein 12 13 14 15 16 It contains a large intracellular cytoplasmic N terminal domain an extreme C terminal transmembrane domain and a short C terminal extracellular domain The cytosolic domain of dysferlin is composed of seven highly conserved C2 domains C2A G which are conserved across several proteins within the ferlin family including dysferlin homolog myoferlin 17 18 13 In fact the C2 domain at any given position is more similar to the C2 domain at the corresponding position within other ferlin family members than the adjacent C2 domain within the same protein This suggests that each individual C2 domain may in fact play a specific role in dysferlin function and each has in fact been shown to be required for two of dysferlin s roles stabilization of calcium signaling and membrane repair 19 Mutations in each of these domains can cause dysferlinopathy A crystal structure of the C2A domain of human dysferlin has been solved and reveals that the C2A domain changes conformation when interacting with calcium ions 13 which is consistent with a growing body of evidence suggesting that the C2A domain plays a role in calcium dependent lipid binding 20 Its ability to stabilize calcium signaling in the intact dysferlin protein depends on its calcium binding activity 21 In addition to the C2 domains dysferlin also contains FerA and DysF domains Mutations in both FerA 22 and DysF 23 can cause muscular dystrophies DysF domain has an interesting structure as in contains one DysF domain within another DysF domain a result of gene duplication however the function of this domain is currently unknown 23 FerA domain is conserved among all members of ferlin protein family FerA domain is a four helix bundle and it can interact with membrane usually in a calcium dependent manner 22 Function editThe most intensively studied role for dysferlin is in a cellular process called membrane repair Membrane repair is a critical mechanism by which cells are able to seal dramatic wounds to the plasma membrane Muscle is thought to be particularly prone to membrane wounds given that muscle cells transmit high force and undergo cycles of contraction Dysferlin is highly expressed in muscle and is homologous to the ferlin family of proteins which are thought to regulate membrane fusion across a wide variety of species and cell types 24 Several lines of evidence suggest that dysferlin may be involved in membrane repair in muscle First dysferlin deficient muscle fibers show accumulation of vesicles which are critical for membrane repair in non muscle cell types near membrane lesions indicating that dysferlin may be required for fusion of repair vesicles with the plasma membrane Further dysferlin deficient muscle fibers take up extracellular dyes to a greater extent than wild type muscle fibers following laser induced wounding in vitro 25 Dysferlin is also markedly enriched at membrane lesions with several additional proteins thought to be involved in membrane resealing including annexin and MG53 26 Exactly how dysferlin contributes to membrane resealing is not clear but biochemical evidence indicates that dysferlin may bind lipids in a calcium dependent manner consistent with a role for dysferlin in regulating fusion of repair vesicles with the sarcolemma during membrane repair 27 Furthermore live cell imaging of dysferlin eGFP expressing myotubes indicates that dysferlin localizes to a cellular compartment that responds to injury by forming large dysferlin containing vesicles and formation of these vesicles may contribute to wound repair 28 Dysferlin may also be involved in Alzheimer s disease pathogenesis 29 Another well studied role for dysferlin is in stabilization of calcium signaling especially following a mild injury This approach was based on two observations that muscle lacking dysferlin that is injured by eccentric contractions can repair its plasma membrane or sarcolemma as efficiently as healthy muscle can 30 and that most of the dysferlin in healthy muscle is concentrated in the transverse tubules at triad junctions 31 32 where calcium release is regulated Destabilization of signaling in dysferlinopathic muscle can result in the generation of calcium waves 33 which can contribute to the disease pathology Nearly every change in dysferlin that affects membrane repair also destabilizes calcium signaling 34 suggesting that these two activities are closely linked Remarkably however membrane repair requires calcium ions whereas calcium ions contribute to the destabilization of signaling when dysferlin is absent or mutated 35 These paradoxical results have yet to be reconciled Interactions editDysferlin has been shown to bind to itself to form dimers and perhaps larger oligomers 36 It can also has been shown to interact with Caveolin 3 in skeletal muscle 37 and this interaction is thought to retain dysferlin within the plasma membrane 38 Dysferlin also interacts with MG53 and a functional interaction between dysferlin caveolin 3 and MG53 is thought to be critical for membrane repair in skeletal muscle 39 References edit a b c GRCh38 Ensembl release 89 ENSG00000135636 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000033788 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Passos Bueno MR Richard I Vainzof M Fougerousse F Weissenbach J Broux O Cohen D Akiyama J Marie SK Carvalho AA May 1993 Evidence of genetic heterogeneity in the autosomal recessive adult forms of limb girdle muscular dystrophy following linkage analysis with 15q probes in Brazilian families Journal of Medical Genetics 30 5 385 7 doi 10 1136 jmg 30 5 385 PMC 1016373 PMID 8320700 Entrez Gene DYSF dysferlin limb girdle muscular dystrophy 2B autosomal recessive Kerr JP Ziman AP Mueller AL et al December 2013 Dysferlin Stabilizes Stress induced Ca2 Signaling in the Transverse Tubule Membrane Proc Natl Acad Sci USA 110 51 20831 20836 Bibcode 2013PNAS 11020831K doi 10 1073 pnas 1307960110 PMC 3870721 PMID 24302765 Kerr JP Ward CW Bloch RJ March 2014 Dysferlin at Transverse Tubules Regulates Ca2 Homeostasis in Skeletal Muscle Frontiers in Physiology 5 89 doi 10 3389 fphys 2014 00089 PMC 3944681 PMID 24639655 Lukyanenko V Muriel JM Bloch RJ August 2017 Coupling of Excitation to Ca2 Release is Modulated by Dysferlin J Physiol 595 15 5191 5207 doi 10 1113 JP274515 PMC 5538227 PMID 8568606 Hofhuis J Bersch K Wagner S Molina C Fakuade FE Iyer LM Streckfuss Bomeke K Toischer K Zelarayan LC Voigt N Nikolaev VO Maier LS Klinge L Thoms S July 2020 Dysferlin links excitation contraction coupling to structure and maintenance of the cardiac transverse axial tubule system Europace 22 7 1119 1131 doi 10 1093 europace euaa093 PMID 32572487 Leiden University Medical Center Center for Human and Clinical Genetics Dysferlin Retrieved 21 June 2007 Kawahara G Serafini PR Myers JA Alexander MS Kunkel LM September 2011 Characterization of zebrafish dysferlin by morpholino knockdown Biochemical and Biophysical Research Communications 413 2 358 363 doi 10 1016 j bbrc 2011 08 105 PMC 4526276 PMID 21893049 a b c Fuson K Rice A Mahling R Snow A Nayak K Shanbhogue P et al January 2014 Alternate splicing of dysferlin C2A confers Ca dependent and Ca independent binding for membrane repair Structure 22 1 104 115 doi 10 1016 j str 2013 10 001 PMC 5993433 PMID 24239457 Demonbreun AR Allen MV Warner JL Barefield DY Krishnan S Swanson KE et al June 2016 Enhanced Muscular Dystrophy from Loss of Dysferlin Is Accompanied by Impaired Annexin A6 Translocation after Sarcolemmal Disruption The American Journal of Pathology 186 6 1610 1622 doi 10 1016 j ajpath 2016 02 005 PMC 4901136 PMID 27070822 Cacciottolo M Numitone G Aurino S Caserta IR Fanin M Politano L et al September 2011 Muscular dystrophy with marked Dysferlin deficiency is consistently caused by primary dysferlin gene mutations European Journal of Human Genetics 19 9 974 980 doi 10 1038 ejhg 2011 70 PMC 3179367 PMID 21522182 Matsuda C Kiyosue K Nishino I Goto Y Hayashi YK October 2015 Dysferlinopathy Fibroblasts Are Defective in Plasma Membrane Repair PLOS Currents 7 doi 10 1371 currents md 5865add2d766f39a0e0411d38a7ba09c PMC 4639325 PMID 26579332 Vafiadaki E Reis A Keers S Harrison R Anderson LV Raffelsberger T et al March 2001 Cloning of the mouse dysferlin gene and genomic characterization of the SJL Dysf mutation NeuroReport 12 3 625 629 doi 10 1097 00001756 200103050 00039 PMID 11234777 S2CID 22800606 Abdullah N Padmanarayana M Marty NJ Johnson CP January 2014 Quantitation of the calcium and membrane binding properties of the C2 domains of dysferlin Biophysical Journal 106 2 382 389 Bibcode 2014BpJ 106 382A doi 10 1016 j bpj 2013 11 4492 PMC 3907215 PMID 24461013 Muriel J Lukyanenko V Kwiatkowski T Bhattacharya S Garman D Weisleder N Bloch RJ April 2022 The C2 domains of dysferlin roles in membrane localization Ca2 signalling and sarcolemmal repair The Journal of Physiology 600 8 1953 1968 doi 10 1113 JP282648 PMC 9285653 PMID 35156706 Therrien C Di Fulvio S Pickles S Sinnreich M March 2009 Characterization of lipid binding specificities of dysferlin C2 domains reveals novel interactions with phosphoinositides Biochemistry 48 11 2377 2384 doi 10 1021 bi802242r PMID 19253956 Lukyanenko V Muriel J Garman D Breydo L Bloch RJ November 2022 Elevated Ca2 at the triad junction underlies dysregulation of Ca2 signaling in dysferlin null skeletal muscle Frontiers in Physiology 13 1032447 doi 10 3389 fphys 2022 1032447 PMC 9669649 PMID 36406982 a b Harsini FM Chebrolu S Fuson KL White MA Rice AM Sutton RB July 2018 FerA is a Membrane Associating Four Helix Bundle Domain in the Ferlin Family of Membrane Fusion Proteins Scientific Reports 8 1 10949 Bibcode 2018NatSR 810949H doi 10 1038 s41598 018 29184 1 PMC 6053371 PMID 30026467 a b Sula A Cole AR Yeats C Orengo C Keep NH January 2014 Crystal structures of the human Dysferlin inner DysF domain BMC Structural Biology 14 3 doi 10 1186 1472 6807 14 3 PMC 3898210 PMID 24438169 Bashir R Britton S Strachan T Keers S Vafiadaki E Lako M Richard I Marchand S Bourg N Argov Z Sadeh M Mahjneh I Marconi G Passos Bueno MR Moreira Ede S Zatz M Beckmann JS Bushby K 1998 A gene related to Caenorhabditis elegans spermatogenesis factor fer 1 is mutated in limb girdle muscular dystrophy type 2B Nat Genet 20 1 37 42 doi 10 1038 1689 PMID 9731527 S2CID 24234676 Bansal D Miyake K Vogel SS Groh S Chen CC Williamson R McNeil PL Campbell KP 2003 Defective membrane repair in dysferlin deficient muscular dystrophy Nature 423 6936 168 72 Bibcode 2003Natur 423 168B doi 10 1038 nature01573 PMID 12736685 S2CID 4402938 Roostalu U Strahle U 2012 In vivo imaging of molecular interactions at damaged sarcolemma Dev Cell 22 3 515 29 doi 10 1016 j devcel 2011 12 008 PMID 22421042 Abdullah N Padmanarayana M Marty NJ Johnson CP 2014 Quantitation of the calcium and membrane binding properties of the C2 domains of dysferlin Biophys J 106 2 382 9 Bibcode 2014BpJ 106 382A doi 10 1016 j bpj 2013 11 4492 PMC 3907215 PMID 24461013 McDade JR Michele DE 2014 Membrane damage induced vesicle vesicle fusion of dysferlin containing vesicles in muscle cells requires microtubules and kinesin Hum Mol Genet 23 7 1677 86 doi 10 1093 hmg ddt557 PMC 3943514 PMID 24203699 Chen JA Wang Q Davis Turak J et al April 2015 A multiancestral genome wide exome array study of Alzheimer disease frontotemporal dementia and progressive supranuclear palsy JAMA Neurology 72 4 414 22 doi 10 1001 jamaneurol 2014 4040 PMC 4397175 PMID 25706306 Roche JA Lovering RM Vanapalli R et al Feb 2010 Extensive Mononuclear Infiltration and Myogenesis Characterize the Recovery of Dysferlin Null Skeletal Muscle from Contraction Induced Injuries Am J Physiol Cell Physiol 298 2 C298 C312 doi 10 1152 ajpcell 00122 2009 PMC 2822489 PMID 9923419 Kerr JP Ziman AP Mueller AL et al December 2013 Dysferlin Stabilizes Stress induced Ca2 Signaling in the Transverse Tubule Membrane Proc Natl Acad Sci USA 110 51 20831 20836 Bibcode 2013PNAS 11020831K doi 10 1073 pnas 1307960110 PMC 3870721 PMID 24302765 Roche JA Lovering RM Vanapalli R et al Feb 2010 Extensive Mononuclear Infiltration and Myogenesis Characterize the Recovery of Dysferlin Null Skeletal Muscle from Contraction Induced Injuries Am J Physiol Cell Physiol 298 2 C298 C312 doi 10 1152 ajpcell 00122 2009 PMC 2822489 PMID 9923419 Lukyanenko V Muriel J Bloch RJ August 2017 Coupling of Excitation to Ca2 Release is Modulated by Dysferlin J Physiol 595 15 5191 5207 doi 10 1113 JP274515 PMC 5538227 PMID 8568606 Muriel J Lukyanenko V Kwiatkowski T et al Apr 2022 The C2 Domains of Dysferlin Roles in Membrane Localization Stabilization of Ca2 Signaling and Membrane Repair J Physiol 600 8 1953 1968 doi 10 1113 JP282648 PMC 9285653 PMID 35156706 Muriel J Lukyanenko V Kwiatkowski T et al Apr 2022 The C2 Domains of Dysferlin Roles in Membrane Localization Stabilization of Ca2 Signaling and Membrane Repair J Physiol 600 8 1953 1968 doi 10 1113 JP282648 PMC 9285653 PMID 35156706 Roche JA Ru L ONeill A et al Nov 2011 Unmasking intracellular dysferlin J Histochem 59 11 964 975 doi 10 1369 0022155411423274 PMC 3261626 PMID 22043020 Matsuda C Hayashi YK Ogawa M Aoki M Murayama K Nishino I Nonaka I Arahata K Brown RH August 2001 The sarcolemmal proteins dysferlin and caveolin 3 interact in skeletal muscle Hum Mol Genet 10 17 1761 6 doi 10 1093 hmg 10 17 1761 PMID 11532985 Hernandez Deviez DJ Howes MT Laval SH Bushby K Hancock JF Parton RG 2008 Caveolin regulates endocytosis of the muscle repair protein dysferlin PDF J Biol Chem 283 10 6476 88 doi 10 1074 jbc M708776200 PMID 18096699 S2CID 8337318 Cai C Weisleder N Ko JK Komazaki S Sunada Y Nishi M Takeshima H Ma J 2009 Membrane repair defects in muscular dystrophy are linked to altered interaction between MG53 caveolin 3 and dysferlin J Biol Chem 284 23 15894 902 doi 10 1074 jbc M109 009589 PMC 2708885 PMID 19380584 Further reading editBejaoui K Hirabayashi K Hentati F Haines JL Ben Hamida C Belal S Miller RG McKenna Yasek D Weissenbach J Rowland LP 1995 Linkage of Miyoshi myopathy distal autosomal recessive muscular dystrophy locus to chromosome 2p12 14 Neurology 45 4 768 72 doi 10 1212 wnl 45 4 768 PMID 7723968 S2CID 31029040 Bashir R Strachan T Keers S Stephenson A Mahjneh I Marconi G Nashef L Bushby KM 1994 A gene for autosomal recessive limb girdle muscular dystrophy maps to chromosome 2p Hum Mol Genet 3 3 455 7 doi 10 1093 hmg 3 3 455 PMID 8012357 Liu J Aoki M Illa I Wu C Fardeau M Angelini C Serrano C Urtizberea JA Hentati F Hamida MB Bohlega S Culper EJ Amato AA Bossie K Oeltjen J Bejaoui K McKenna Yasek D Hosler BA Schurr E Arahata K de Jong PJ Brown RH 1998 Dysferlin a novel skeletal muscle gene is mutated in Miyoshi myopathy and limb girdle muscular dystrophy Nat Genet 20 1 31 6 doi 10 1038 1682 PMID 9731526 S2CID 12018395 Bashir R Britton S Strachan T Keers S Vafiadaki E Lako M Richard I Marchand S Bourg N Argov Z Sadeh M Mahjneh I Marconi G Passos Bueno MR Moreira Ede S Zatz M Beckmann JS Bushby K 1998 A gene related to Caenorhabditis elegans spermatogenesis factor fer 1 is mutated in limb girdle muscular dystrophy type 2B Nat Genet 20 1 37 42 doi 10 1038 1689 PMID 9731527 S2CID 24234676 Anderson LV Davison K Moss JA Young C Cullen MJ Walsh J Johnson MA Bashir R Britton S Keers S Argov Z Mahjneh I Fougerousse F Beckmann JS Bushby KM 1999 Dysferlin is a plasma membrane protein and is expressed early in human development Hum Mol Genet 8 5 855 61 doi 10 1093 hmg 8 5 855 PMID 10196375 Weiler T Bashir R Anderson LV Davison K Moss JA Britton S Nylen E Keers S Vafiadaki E Greenberg CR Bushby CR Wrogemann K 1999 Identical mutation in patients with limb girdle muscular dystrophy type 2B or Miyoshi myopathy suggests a role for modifier gene s Hum Mol Genet 8 5 871 7 doi 10 1093 hmg 8 5 871 PMID 10196377 Matsuda C Aoki M Hayashi YK Ho MF Arahata K Brown RH 1999 Dysferlin is a surface membrane associated protein that is absent in Miyoshi myopathy Neurology 53 5 1119 22 doi 10 1212 wnl 53 5 1119 PMID 10496277 S2CID 6068681 Illa I Serrano Munuera C Gallardo E Lasa A Rojas Garcia R Palmer J Gallano P Baiget M Matsuda C Brown RH 2001 Distal anterior compartment myopathy a dysferlin mutation causing a new muscular dystrophy phenotype Ann Neurol 49 1 130 4 doi 10 1002 1531 8249 200101 49 1 lt 130 AID ANA22 gt 3 0 CO 2 0 PMID 11198284 S2CID 9278818 Aoki M Liu J Richard I Bashir R Britton S Keers SM Oeltjen J Brown HE Marchand S Bourg N Beley C McKenna Yasek D Arahata K Bohlega S Cupler E Illa I Majneh I Barohn RJ Urtizberea JA Fardeau M Amato A Angelini C Bushby K Beckmann JS Brown RH 2001 Genomic organization of the dysferlin gene and novel mutations in Miyoshi myopathy Neurology 57 2 271 8 doi 10 1212 wnl 57 2 271 PMID 11468312 S2CID 31959549 Matsuda C Hayashi YK Ogawa M Aoki M Murayama K Nishino I Nonaka I Arahata K Brown RH 2001 The sarcolemmal proteins dysferlin and caveolin 3 interact in skeletal muscle Hum Mol Genet 10 17 1761 6 doi 10 1093 hmg 10 17 1761 PMID 11532985 Ikezoe K Furuya H Ohyagi Y Osoegawa M Nishino I Nonaka I Kira J 2003 Dysferlin expression in tubular aggregates their possible relationship to endoplasmic reticulum stress Acta Neuropathol 105 6 603 9 doi 10 1007 s00401 003 0686 1 PMID 12664320 S2CID 7734282 von Tell D Bruder CE Anderson LV Anvret M Ahlberg G 2003 Refined mapping of the Welander distal myopathy region on chromosome 2p13 positions the new candidate region telomeric of the DYSF locus Neurogenetics 4 4 173 7 doi 10 1007 s10048 003 0154 z PMID 12836053 S2CID 27539044 Lennon NJ Kho A Bacskai BJ Perlmutter SL Hyman BT Brown RH 2003 Dysferlin interacts with annexins A1 and A2 and mediates sarcolemmal wound healing J Biol Chem 278 50 50466 73 doi 10 1074 jbc M307247200 PMID 14506282 Katz JS Rando TA Barohn RJ Saperstein DS Jackson CE Wicklund M Amato AA 2003 Late onset distal muscular dystrophy affecting the posterior calves Muscle Nerve 28 4 443 8 doi 10 1002 mus 10458 PMID 14506716 S2CID 29825709 Confalonieri P Oliva L Andreetta F Lorenzoni R Dassi P Mariani E Morandi L Mora M Cornelio F Mantegazza R 2003 Muscle inflammation and MHC class I up regulation in muscular dystrophy with lack of dysferlin an immunopathological study J Neuroimmunol 142 1 2 130 6 doi 10 1016 S0165 5728 03 00255 8 PMID 14512171 S2CID 37727809 Foxton RM Laval SH Bushby KM 2004 Characterisation of the dysferlin skeletal muscle promoter Eur J Hum Genet 12 2 127 31 doi 10 1038 sj ejhg 5201092 PMID 14560310 Cagliani R Fortunato F Giorda R Rodolico C Bonaglia MC Sironi M D Angelo MG Prelle A Locatelli F Toscano A Bresolin N Comi GP 2003 Molecular analysis of LGMD 2B and MM patients identification of novel DYSF mutations and possible founder effect in the Italian population Neuromuscul Disord 13 10 788 95 doi 10 1016 S0960 8966 03 00133 0 PMID 14678801 S2CID 23179310 Capanni C Sabatelli P Mattioli E Ognibene A Columbaro M Lattanzi G Merlini L Minetti C Maraldi NM Squarzoni S 2003 Dysferlin in a hyperCKaemic patient with caveolin 3 mutation and in C2C12 cells after p38 MAP kinase inhibition Exp Mol Med 35 6 538 44 doi 10 1038 emm 2003 70 PMID 14749532 Bruss M Homann J Molderings GJ 2004 Dysferlinopathy as an extrahepatic cause for the elevation of serum transaminases Med Klin Munich 99 6 326 9 doi 10 1007 s00063 004 1046 1 PMID 15221058 S2CID 30657667 Huang Y de Morree A van Remoortere A Bushby K Frants RR den Dunnen JT van der Maarel SM 2008 Calpain 3 is a modulator of the dysferlin protein complex in skeletal muscle Hum Mol Genet 17 12 1855 66 doi 10 1093 hmg ddn081 PMC 2900895 PMID 18334579 External links editGeneReviews NCBI NIH UW entry on Dysferlinopathy including Miyoshi Distal Myopathy Miyoshi Myopathy Limb Girdle Muscular Dystrophy Type 2B LGMD2B LOVD mutation database DYSF Retrieved from https en wikipedia org w index php title Dysferlin amp oldid 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