Myelin-associated glycoprotein (MAG, Siglec-4) is a type 1 transmembrane proteinglycoprotein localized in periaxonal Schwann cell and oligodendrocyte membranes, where it plays a role in glial-axonal interactions. MAG is a member of the SIGLEC family of proteins and is a functional ligand of the NOGO-66 receptor, NgR.[5] MAG is believed to be involved in myelination during nerve regeneration in the PNS[6] and is vital for the long-term survival of the myelinated axons following myelinogenesis.[7] In the CNS MAG is one of three main myelin-associated inhibitors of axonal regeneration after injury,[8] making it an important protein for future research on neurogenesis in the CNS.
MAG is a 100 kDA glycoprotein.[9] Uncleaved MAG is a complete transmembrane form, which acts as a signaling and adhesion molecule.[10] MAG can also act as a signaling molecule as a soluble protein after it has been proteolytically shed. This form of the protein is called dMAG.[11]
Adhesionedit
MAG has an extended conformation of five immunoglobulin (Ig) domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5. MAG-oligosaccharide complex structures and biophysical assays show how MAG engages axonal gangliosides at domain Ig1.[12]
Functionedit
Myelin-axon interactionsedit
MAG is a critical protein in the formation and maintenance of myelin sheaths. MAG is localized on the inner membrane of the myelin sheath and interacts with axonal membrane proteins to attach the myelin sheath to the axon.[13].\ Mutations to the MAG gene are implicated in demyelination diseases such as multiple sclerosis.[14]
Inhibition of nerve regenerationedit
Axons in the central nervous system do not regenerate after injury the same way that axons in the peripheral nervous system do. [15] The mechanism responsible for inhibited neuroregeneration is regulated by three main proteins, one of which is MAG.[16][17] The exact mechanism through which MAG inhibits neuroregeneration appears to be through binding of NgR. This receptor is also bound by Nogo protein, suggesting that the mechanism of myelin-associated inhibition of axon regeneration through NgR the has redundant ligands[clarification needed], furthering the inhibition.[18] MAG binds with high affinity to NgR, suggesting that it is equally as responsible for inhibition of axon regeneration as Nogo.[19]
Rho kinase pathwayedit
Once MAG (or Nogo) has bound to NgR, NgR activates the rho kinase (ROCK) pathway. The activation of the rho kinase pathway leads to the phosphorylation of proteins which inhibit neurite outgrowth.[20]
^Barton DE, Arquint M, Roder J, Dunn R, Francke U (October 1987). "The myelin-associated glycoprotein gene: mapping to human chromosome 19 and mouse chromosome 7 and expression in quivering mice". Genomics. 1 (2): 107–12. doi:10.1016/0888-7543(87)90002-4. PMID 2447011.
^McKerracher L, David S, Jackson DL, Kottis V, Dunn RJ, Braun PE (October 1994). "Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth". Neuron. 13 (4): 805–11. doi:10.1016/0896-6273(94)90247-x. PMID 7524558. S2CID 28429007.
^Lopez PH (2014). "Role of myelin-associated glycoprotein (siglec-4a) in the nervous system". Advances in Neurobiology. 9: 245–62. doi:10.1007/978-1-4939-1154-7_11. ISBN978-1-4939-1153-0. PMID 25151382.
^Vinson M, Strijbos PJ, Rowles A, Facci L, Moore SE, Simmons DL, Walsh FS (June 2001). "Myelin-associated glycoprotein interacts with ganglioside GT1b. A mechanism for neurite outgrowth inhibition". The Journal of Biological Chemistry. 276 (23): 20280–5. doi:10.1074/jbc.M100345200. PMID 11279053.
^Tang S, Shen YJ, DeBellard ME, Mukhopadhyay G, Salzer JL, Crocker PR, Filbin MT (September 1997). "Myelin-associated glycoprotein interacts with neurons via a sialic acid binding site at ARG118 and a distinct neurite inhibition site". The Journal of Cell Biology. 138 (6): 1355–66. doi:10.1083/jcb.138.6.1355. PMC2132563. PMID 9298990.
^Gage FH, Temple S (October 2013). "Neural stem cells: generating and regenerating the brain". Neuron. 80 (3): 588–601. doi:10.1016/j.neuron.2013.10.037. PMID 24183012.
^McKerracher L, David S, Jackson DL, Kottis V, Dunn RJ, Braun PE (October 1994). "Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth". Neuron. 13 (4): 805–11. doi:10.1016/0896-6273(94)90247-x. PMID 7524558. S2CID 28429007.
^Mukhopadhyay G, Doherty P, Walsh FS, Crocker PR, Filbin MT (September 1994). "A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration". Neuron. 13 (3): 757–67. doi:10.1016/0896-6273(94)90042-6. PMID 7522484. S2CID 928929.
^Domeniconi M, Cao Z, Spencer T, Sivasankaran R, Wang K, Nikulina E, Kimura N, Cai H, Deng K, Gao Y, He Z, Filbin M (July 2002). "Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth". Neuron. 35 (2): 283–90. doi:10.1016/s0896-6273(02)00770-5. PMID 12160746. S2CID 17970421.
^Liu BP, Fournier A, GrandPré T, Strittmatter SM (August 2002). "Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor". Science. 297 (5584): 1190–3. Bibcode:2002Sci...297.1190L. doi:10.1126/science.1073031. PMID 12089450. S2CID 1357777.
^Kaplan DR, Miller FD (May 2003). "Axon growth inhibition: signals from the p75 neurotrophin receptor". Nature Neuroscience. 6 (5): 435–6. doi:10.1038/nn0503-435. PMID 12715005. S2CID 40563260.
This article on a gene on human chromosome 19 is a stub. You can help Wikipedia by expanding it.
myelin, associated, glycoprotein, siglec, type, transmembrane, protein, glycoprotein, localized, periaxonal, schwann, cell, oligodendrocyte, membranes, where, plays, role, glial, axonal, interactions, member, siglec, family, proteins, functional, ligand, nogo,. Myelin associated glycoprotein MAG Siglec 4 is a type 1 transmembrane protein glycoprotein localized in periaxonal Schwann cell and oligodendrocyte membranes where it plays a role in glial axonal interactions MAG is a member of the SIGLEC family of proteins and is a functional ligand of the NOGO 66 receptor NgR 5 MAG is believed to be involved in myelination during nerve regeneration in the PNS 6 and is vital for the long term survival of the myelinated axons following myelinogenesis 7 In the CNS MAG is one of three main myelin associated inhibitors of axonal regeneration after injury 8 making it an important protein for future research on neurogenesis in the CNS MAGIdentifiersAliasesMAG GMA S SIGLEC 4A SIGLEC4A SPG75 myelin associated glycoproteinExternal IDsOMIM 159460 MGI 96912 HomoloGene 1771 GeneCards MAGGene location Human Chr Chromosome 19 human 1 Band19q13 12Start35 292 125 bp 1 End35 313 807 bp 1 Gene location Mouse Chr Chromosome 7 mouse 2 Band7 B1 7 19 26 cMStart30 598 601 bp 2 End30 614 298 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed ininferior ganglion of vagus nervemiddle frontal gyruscorpus callosumponssuperior vestibular nucleussubthalamic nucleusexternal globus pallidusventral tegmental areaputamenBrodmann area 10Top expressed inpontine nucleilateral geniculate nucleusglobus pallidusdorsal tegmental nucleusventral tegmental areamedulla oblongatamedial geniculate nucleussuperior colliculuscerebellar cortexinferior colliculusMore reference expression dataBioGPSn aGene ontologyMolecular functionsignaling receptor binding lipid binding protein kinase binding carbohydrate binding sialic acid binding protein homodimerization activity ganglioside GT1b bindingCellular componentcytoplasm plasma membrane integral component of plasma membrane membrane integral component of membrane paranode region of axon myelin sheath adaxonal region myelin sheath compact myelin Schmidt Lanterman incisure membrane raft mesaxonBiological processcell adhesion nervous system development negative regulation of neuron projection development substantia nigra development central nervous system myelination negative regulation of axon extension positive regulation of myelination negative regulation of neuron apoptotic process negative regulation of neuron differentiation positive regulation of astrocyte differentiation negative regulation of axonogenesis leukocyte migration cellular response to mechanical stimulus cell cell adhesion via plasma membrane adhesion molecules transmission of nerve impulse axon regenerationSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez409917136EnsemblENSG00000105695ENSMUSG00000036634UniProtP20916P20917RefSeq mRNA NM 080600NM 001199216NM 002361NM 010758NM 001346084NM 001346085NM 001346086NM 001346087NM 001346088NM 001346089NM 001369262RefSeq protein NP 001186145NP 002352NP 542167NP 001333013NP 001333014NP 001333015NP 001333016NP 001333017NP 001333018NP 034888NP 001356191Location UCSC Chr 19 35 29 35 31 MbChr 7 30 6 30 61 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Structure 1 1 Adhesion 2 Function 2 1 Myelin axon interactions 2 2 Inhibition of nerve regeneration 2 3 Rho kinase pathway 3 See also 4 External links 5 ReferencesStructure editMAG is a 100 kDA glycoprotein 9 Uncleaved MAG is a complete transmembrane form which acts as a signaling and adhesion molecule 10 MAG can also act as a signaling molecule as a soluble protein after it has been proteolytically shed This form of the protein is called dMAG 11 Adhesion edit MAG has an extended conformation of five immunoglobulin Ig domains and a homodimeric arrangement involving membrane proximal domains Ig4 and Ig5 MAG oligosaccharide complex structures and biophysical assays show how MAG engages axonal gangliosides at domain Ig1 12 Function editMyelin axon interactions edit MAG is a critical protein in the formation and maintenance of myelin sheaths MAG is localized on the inner membrane of the myelin sheath and interacts with axonal membrane proteins to attach the myelin sheath to the axon 13 Mutations to the MAG gene are implicated in demyelination diseases such as multiple sclerosis 14 Inhibition of nerve regeneration edit Axons in the central nervous system do not regenerate after injury the same way that axons in the peripheral nervous system do 15 The mechanism responsible for inhibited neuroregeneration is regulated by three main proteins one of which is MAG 16 17 The exact mechanism through which MAG inhibits neuroregeneration appears to be through binding of NgR This receptor is also bound by Nogo protein suggesting that the mechanism of myelin associated inhibition of axon regeneration through NgR the has redundant ligands clarification needed furthering the inhibition 18 MAG binds with high affinity to NgR suggesting that it is equally as responsible for inhibition of axon regeneration as Nogo 19 Rho kinase pathway edit Once MAG or Nogo has bound to NgR NgR activates the rho kinase ROCK pathway The activation of the rho kinase pathway leads to the phosphorylation of proteins which inhibit neurite outgrowth 20 See also editMyelin Myelinogenesis NgR Myelin oligodendrocyte glycoprotein Anti MAG peripheral neuropathyExternal links editMyelin associated glycoprotein at the U S National Library of Medicine Medical Subject Headings MeSH References edit a b c GRCh38 Ensembl release 89 ENSG00000105695 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000036634 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 Quarles RH March 2007 Myelin associated glycoprotein MAG past present and beyond Journal of Neurochemistry 100 6 1431 48 doi 10 1111 j 1471 4159 2006 04319 x PMID 17241126 S2CID 1544418 Barton DE Arquint M Roder J Dunn R Francke U October 1987 The myelin associated glycoprotein gene mapping to human chromosome 19 and mouse chromosome 7 and expression in quivering mice Genomics 1 2 107 12 doi 10 1016 0888 7543 87 90002 4 PMID 2447011 Bjartmar C Yin X Trapp BD 1999 Axonal pathology in myelin disorders Journal of Neurocytology 28 4 5 383 95 doi 10 1023 a 1007010205037 PMID 10739578 S2CID 40528071 McKerracher L David S Jackson DL Kottis V Dunn RJ Braun PE October 1994 Identification of myelin associated glycoprotein as a major myelin derived inhibitor of neurite growth Neuron 13 4 805 11 doi 10 1016 0896 6273 94 90247 x PMID 7524558 S2CID 28429007 Lopez PH 2014 Role of myelin associated glycoprotein siglec 4a in the nervous system Advances in Neurobiology 9 245 62 doi 10 1007 978 1 4939 1154 7 11 ISBN 978 1 4939 1153 0 PMID 25151382 Vinson M Strijbos PJ Rowles A Facci L Moore SE Simmons DL Walsh FS June 2001 Myelin associated glycoprotein interacts with ganglioside GT1b A mechanism for neurite outgrowth inhibition The Journal of Biological Chemistry 276 23 20280 5 doi 10 1074 jbc M100345200 PMID 11279053 Tang S Shen YJ DeBellard ME Mukhopadhyay G Salzer JL Crocker PR Filbin MT September 1997 Myelin associated glycoprotein interacts with neurons via a sialic acid binding site at ARG118 and a distinct neurite inhibition site The Journal of Cell Biology 138 6 1355 66 doi 10 1083 jcb 138 6 1355 PMC 2132563 PMID 9298990 Pronker MF Lemstra S Snijder J Heck AJ Thies Weesie DM Pasterkamp RJ Janssen BJ December 2016 Structural basis of myelin associated glycoprotein adhesion and signalling Nature Communications 7 13584 Bibcode 2016NatCo 713584P doi 10 1038 ncomms13584 PMC 5150538 PMID 27922006 Lopez PH 2014 Role of myelin associated glycoprotein siglec 4a in the nervous system Advances in Neurobiology 9 245 62 doi 10 1007 978 1 4939 1154 7 11 ISBN 978 1 4939 1153 0 PMID 25151382 Pronker MF Lemstra S Snijder J Heck AJ Thies Weesie DM Pasterkamp RJ Janssen BJ December 2016 Structural basis of myelin associated glycoprotein adhesion and signalling Nature Communications 7 13584 Bibcode 2016NatCo 713584P doi 10 1038 ncomms13584 PMC 5150538 PMID 27922006 Gage FH Temple S October 2013 Neural stem cells generating and regenerating the brain Neuron 80 3 588 601 doi 10 1016 j neuron 2013 10 037 PMID 24183012 McKerracher L David S Jackson DL Kottis V Dunn RJ Braun PE October 1994 Identification of myelin associated glycoprotein as a major myelin derived inhibitor of neurite growth Neuron 13 4 805 11 doi 10 1016 0896 6273 94 90247 x PMID 7524558 S2CID 28429007 Mukhopadhyay G Doherty P Walsh FS Crocker PR Filbin MT September 1994 A novel role for myelin associated glycoprotein as an inhibitor of axonal regeneration Neuron 13 3 757 67 doi 10 1016 0896 6273 94 90042 6 PMID 7522484 S2CID 928929 Domeniconi M Cao Z Spencer T Sivasankaran R Wang K Nikulina E Kimura N Cai H Deng K Gao Y He Z Filbin M July 2002 Myelin associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth Neuron 35 2 283 90 doi 10 1016 s0896 6273 02 00770 5 PMID 12160746 S2CID 17970421 Liu BP Fournier A GrandPre T Strittmatter SM August 2002 Myelin associated glycoprotein as a functional ligand for the Nogo 66 receptor Science 297 5584 1190 3 Bibcode 2002Sci 297 1190L doi 10 1126 science 1073031 PMID 12089450 S2CID 1357777 Kaplan DR Miller FD May 2003 Axon growth inhibition signals from the p75 neurotrophin receptor Nature Neuroscience 6 5 435 6 doi 10 1038 nn0503 435 PMID 12715005 S2CID 40563260 nbsp This article on a gene on human chromosome 19 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title Myelin associated glycoprotein amp oldid 1171076984, wikipedia, wiki, book, books, library,
