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• W2023800912 abstract "Mutations in the ankyrin repeat domain (ARD) of TRPV4 are responsible for several channelopathies, including Charcot–Marie–Tooth disease type 2C and congenital distal and scapuloperoneal spinal muscular atrophy. However, the molecular pathogenesis mediated by these mutations remains elusive, mainly due to limited understanding of the TRPV4 ARD function. Here we show that phosphoinositide binding to the TRPV4 ARD leads to suppression of the channel activity. Among the phosphoinositides, phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) most potently binds to the TRPV4 ARD. The crystal structure of the TRPV4 ARD in complex with inositol-1,4,5-trisphosphate, the head-group of PI(4,5)P2, and the molecular-dynamics simulations revealed the PI(4,5)P2-binding amino-acid residues. The TRPV4 channel activities were increased by titration or hydrolysis of membrane PI(4,5)P2. Notably, disease-associated TRPV4 mutations that cause a gain-of-function phenotype abolished PI(4,5)P2 binding and PI(4,5)P2 sensitivity. These findings identify TRPV4 ARD as a lipid-binding domain in which interactions with PI(4,5)P2 normalize the channel activity in TRPV4. Mutations in the ankyrin repeat domain (ARD) of TRPV4 are responsible for several channelopathies but little is known about the physiological function of this domain. Here the authors show that phosphoinositide binding to TRPV4 ARD leads to suppression of the channel activity, and obtain the crystal structure of the domain in complex with inositol-1,4,5-trisphosphate." @default.
• W2023800912 created "2016-06-24" @default.
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• W2023800912 date "2014-09-26" @default.
• W2023800912 modified "2023-10-16" @default.
• W2023800912 title "TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P2" @default.
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• W2023800912 cites W1571058997 @default.
• W2023800912 cites W1668450698 @default.
• W2023800912 cites W1707717597 @default.
• W2023800912 cites W1968668235 @default.
• W2023800912 cites W1968683511 @default.
• W2023800912 cites W1969493239 @default.
• W2023800912 cites W1969599787 @default.
• W2023800912 cites W1970356391 @default.
• W2023800912 cites W1973643499 @default.
• W2023800912 cites W1973796039 @default.
• W2023800912 cites W1975517707 @default.
• W2023800912 cites W1979579389 @default.
• W2023800912 cites W1980198222 @default.
• W2023800912 cites W1981411461 @default.
• W2023800912 cites W1985207083 @default.
• W2023800912 cites W1985474963 @default.
• W2023800912 cites W1986074692 @default.
• W2023800912 cites W1986972844 @default.
• W2023800912 cites W1988759455 @default.
• W2023800912 cites W1988919269 @default.
• W2023800912 cites W1992071366 @default.
• W2023800912 cites W1992601827 @default.
• W2023800912 cites W1993871865 @default.
• W2023800912 cites W1996437447 @default.
• W2023800912 cites W1999825570 @default.
• W2023800912 cites W2003380041 @default.
• W2023800912 cites W2015174816 @default.
• W2023800912 cites W2020176916 @default.
• W2023800912 cites W2027408247 @default.
• W2023800912 cites W2027842776 @default.
• W2023800912 cites W2043312574 @default.
• W2023800912 cites W2050333027 @default.
• W2023800912 cites W2054799935 @default.
• W2023800912 cites W2056197841 @default.
• W2023800912 cites W2057198489 @default.
• W2023800912 cites W2065155413 @default.
• W2023800912 cites W2066414494 @default.
• W2023800912 cites W2067265041 @default.
• W2023800912 cites W2070023044 @default.
• W2023800912 cites W2070948590 @default.
• W2023800912 cites W2072459093 @default.
• W2023800912 cites W2076542693 @default.
• W2023800912 cites W2078762945 @default.
• W2023800912 cites W2084938664 @default.
• W2023800912 cites W2086524338 @default.
• W2023800912 cites W2092249847 @default.
• W2023800912 cites W2105668062 @default.
• W2023800912 cites W2108305553 @default.
• W2023800912 cites W2109184569 @default.
• W2023800912 cites W2115607358 @default.
• W2023800912 cites W2117724788 @default.
• W2023800912 cites W2123553276 @default.
• W2023800912 cites W2128158693 @default.
• W2023800912 cites W2135741627 @default.
• W2023800912 cites W2137572745 @default.
• W2023800912 cites W2137994842 @default.
• W2023800912 cites W2143878771 @default.
• W2023800912 cites W2144081223 @default.
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• W2023800912 cites W2159457567 @default.
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• W2023800912 doi "https://doi.org/10.1038/ncomms5994" @default.
• W2023800912 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25256292" @default.
• W2023800912 hasPublicationYear "2014" @default.
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