Phosphatidylinositol 4,5-bisphosphate (PIP2) is an anionic signaling lipid. Its polyunsaturated acyl chains exclude it from GM1 lipid rafts.[5][6] The multiple negative charges on PIP2 are thought to cluster proteins with positive charges residing in the plasma membrane leading to nanoscale clusters. PIP3 is also clustered away from PIP2 and away from GM1 lipid rafts.
Biological functionedit
PIP2 domains inhibit GM1 domain function by attracting palmitoylated proteins away from GM1 lipid rafts.[7] For this to occur a protein must be both palmitoylated and bind PIP2. Presumably PIP2 could also antagonize PIP3 localization but this has not been shown directly.
PLD2edit
Phospholipase D2 (PLD2) binds PIP2 and localizes with lipid rafts. Increases in cholesterol overcome PIP2 binding and sequester PLD2 into GM1 lipid rafts away from its substrate phosphatidylcholine. Efflux of cholesterol causes PLD2 to translocate to PIP2 domains where it is activated by substrate presentation.[8] Both PIP2 signaling and cholesterol signaling regulate the enzyme.
ACE2 receptoredit
Angiotensin converting enzyme (ACE2) is regulated by PIP2 localization. The ACE2 enzyme is palmitoylated which drives the protein into GM1 lipids. The enzyme also bind to PIP2 which moves it out of the endocytic pathway. The drug hydroxychloroquine blocks ACE2 interaction with PIP2 in multiple cell types shifting its localization.[9]
^Levental, Ilya; Christian, David A.; Wang, Yu-Hsiu; Madara, Jonathan J.; Discher, Dennis E.; Janmey, Paul A. (1 September 2009). "Calcium-Dependent Lateral Organization in Phosphatidylinositol 4,5-Bisphosphate (PIP2)- and Cholesterol-Containing Monolayers". Biochemistry. 48 (34): 8241–8248. doi:10.1021/bi9007879. PMC2774806. PMID 19630438.
^van den Bogaart, G; Meyenberg, K; Risselada, HJ; Amin, H; Willig, KI; Hubrich, BE; Dier, M; Hell, SW; Grubmüller, H; Diederichsen, U; Jahn, R (23 October 2011). "Membrane protein sequestering by ionic protein-lipid interactions". Nature. 479 (7374): 552–5. Bibcode:2011Natur.479..552V. doi:10.1038/nature10545. PMC3409895. PMID 22020284.
^Wang, J; Richards, DA (15 September 2012). "Segregation of PIP2 and PIP3 into distinct nanoscale regions within the plasma membrane". Biology Open. 1 (9): 857–62. doi:10.1242/bio.20122071. PMC3507238. PMID 23213479.
^Robinson, CV; Rohacs, T; Hansen, SB (September 2019). "Tools for Understanding Nanoscale Lipid Regulation of Ion Channels". Trends in Biochemical Sciences. 44 (9): 795–806. doi:10.1016/j.tibs.2019.04.001. PMC6729126. PMID 31060927.
^Milne, SB; Ivanova, PT; DeCamp, D; Hsueh, RC; Brown, HA (August 2005). "A targeted mass spectrometric analysis of phosphatidylinositol phosphate species". Journal of Lipid Research. 46 (8): 1796–802. doi:10.1194/jlr.D500010-JLR200. PMID 15897608. S2CID 45134413.
^Hansen, SB (May 2015). "Lipid agonism: The PIP2 paradigm of ligand-gated ion channels". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1851 (5): 620–8. doi:10.1016/j.bbalip.2015.01.011. PMC4540326. PMID 25633344.
^Robinson, CV; Rohacs, T; Hansen, SB (September 2019). "Tools for Understanding Nanoscale Lipid Regulation of Ion Channels". Trends in Biochemical Sciences. 44 (9): 795–806. doi:10.1016/j.tibs.2019.04.001. PMC6729126. PMID 31060927.
^Petersen, EN; Chung, HW; Nayebosadri, A; Hansen, SB (15 December 2016). "Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D." Nature Communications. 7: 13873. Bibcode:2016NatCo...713873P. doi:10.1038/ncomms13873. PMC5171650. PMID 27976674.
pip2, domain, this, article, needs, additional, citations, verification, please, help, improve, this, article, adding, citations, reliable, sources, unsourced, material, challenged, removed, find, sources, news, newspapers, books, scholar, jstor, june, 2020, l. This article needs additional citations for verification Please help improve this article by adding citations to reliable sources Unsourced material may be challenged and removed Find sources PIP2 domain news newspapers books scholar JSTOR June 2020 Learn how and when to remove this message PIP2 domains 1 also called PIP2 clusters are a type of cholesterol independent lipid domain formed from phosphatidylinositol and positively charged proteins in the plasma membrane 2 3 They tend to inhibit GM1 lipid raft function 4 Contents 1 Chemical properties 2 Biological function 2 1 PLD2 2 2 ACE2 receptor 3 Other 4 ReferencesChemical properties editPhosphatidylinositol 4 5 bisphosphate PIP2 is an anionic signaling lipid Its polyunsaturated acyl chains exclude it from GM1 lipid rafts 5 6 The multiple negative charges on PIP2 are thought to cluster proteins with positive charges residing in the plasma membrane leading to nanoscale clusters PIP3 is also clustered away from PIP2 and away from GM1 lipid rafts Biological function editPIP2 domains inhibit GM1 domain function by attracting palmitoylated proteins away from GM1 lipid rafts 7 For this to occur a protein must be both palmitoylated and bind PIP2 Presumably PIP2 could also antagonize PIP3 localization but this has not been shown directly PLD2 edit Phospholipase D2 PLD2 binds PIP2 and localizes with lipid rafts Increases in cholesterol overcome PIP2 binding and sequester PLD2 into GM1 lipid rafts away from its substrate phosphatidylcholine Efflux of cholesterol causes PLD2 to translocate to PIP2 domains where it is activated by substrate presentation 8 Both PIP2 signaling and cholesterol signaling regulate the enzyme ACE2 receptor edit Angiotensin converting enzyme ACE2 is regulated by PIP2 localization The ACE2 enzyme is palmitoylated which drives the protein into GM1 lipids The enzyme also bind to PIP2 which moves it out of the endocytic pathway The drug hydroxychloroquine blocks ACE2 interaction with PIP2 in multiple cell types shifting its localization 9 Other editPIP2 binding proteins PH domain PIP2 palmitate proteins GABAA receptorReferences edit Levental Ilya Christian David A Wang Yu Hsiu Madara Jonathan J Discher Dennis E Janmey Paul A 1 September 2009 Calcium Dependent Lateral Organization in Phosphatidylinositol 4 5 Bisphosphate PIP2 and Cholesterol Containing Monolayers Biochemistry 48 34 8241 8248 doi 10 1021 bi9007879 PMC 2774806 PMID 19630438 van den Bogaart G Meyenberg K Risselada HJ Amin H Willig KI Hubrich BE Dier M Hell SW Grubmuller H Diederichsen U Jahn R 23 October 2011 Membrane protein sequestering by ionic protein lipid interactions Nature 479 7374 552 5 Bibcode 2011Natur 479 552V doi 10 1038 nature10545 PMC 3409895 PMID 22020284 Wang J Richards DA 15 September 2012 Segregation of PIP2 and PIP3 into distinct nanoscale regions within the plasma membrane Biology Open 1 9 857 62 doi 10 1242 bio 20122071 PMC 3507238 PMID 23213479 Robinson CV Rohacs T Hansen SB September 2019 Tools for Understanding Nanoscale Lipid Regulation of Ion Channels Trends in Biochemical Sciences 44 9 795 806 doi 10 1016 j tibs 2019 04 001 PMC 6729126 PMID 31060927 Milne SB Ivanova PT DeCamp D Hsueh RC Brown HA August 2005 A targeted mass spectrometric analysis of phosphatidylinositol phosphate species Journal of Lipid Research 46 8 1796 802 doi 10 1194 jlr D500010 JLR200 PMID 15897608 S2CID 45134413 Hansen SB May 2015 Lipid agonism The PIP2 paradigm of ligand gated ion channels Biochimica et Biophysica Acta BBA Molecular and Cell Biology of Lipids 1851 5 620 8 doi 10 1016 j bbalip 2015 01 011 PMC 4540326 PMID 25633344 Robinson CV Rohacs T Hansen SB September 2019 Tools for Understanding Nanoscale Lipid Regulation of Ion Channels Trends in Biochemical Sciences 44 9 795 806 doi 10 1016 j tibs 2019 04 001 PMC 6729126 PMID 31060927 Petersen EN Chung HW Nayebosadri A Hansen SB 15 December 2016 Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D Nature Communications 7 13873 Bibcode 2016NatCo 713873P doi 10 1038 ncomms13873 PMC 5171650 PMID 27976674 Yuan Z Pavel MA Wang H Kwachukwu JC Mediouni S Jablonski JA Nettles KW Reddy CB Valente ST Hansen SB 14 September 2022 Hydroxychloroquine blocks SARS CoV 2 entry into the endocytic pathway in mammalian cell culture Communications Biology 5 1 958 doi 10 1038 s42003 022 03841 8 PMC 9472185 PMID 36104427 Retrieved from https en wikipedia org w index php title PIP2 domain amp oldid 1168198838, wikipedia, wiki, book, books, library,
