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dc.contributor.author Park, Cheon-Gyu -
dc.contributor.author Park, Yongsoo -
dc.contributor.author Suh, Byung-Chang -
dc.date.available 2017-08-10T08:17:43Z -
dc.date.created 2017-08-09 -
dc.date.issued 2017-02 -
dc.identifier.issn 0022-1295 -
dc.identifier.uri http://hdl.handle.net/20.500.11750/4242 -
dc.description.abstract The β subunit of voltage-gated Ca2+ (CaV) channels plays an important role in regulating gating of the a1 pore-forming subunit and its regulation by phosphatidylinositol 4,5-bisphosphate (PIP2). Subcellular localization of the CaV β subunit is critical for this effect; N-terminal-dependent membrane targeting of the β subunit slows inactivation and decreases PIP2 sensitivity. Here, we provide evidence that the HOOK region of the β subunit plays an important role in the regulation of CaV biophysics. Based on amino acid composition, we broadly divide the HOOK region into three domains: S (polyserine), A (polyacidic), and B (polybasic). We show that a β subunit containing only its A domain in the HOOK region increases inactivation kinetics and channel inhibition by PIP2 depletion, whereas a β subunit with only a B domain decreases these responses. When both the A and B domains are deleted, or when the entire HOOK region is deleted, the responses are elevated. Using a peptide-to-liposome binding assay and confocal microscopy, we find that the B domain of the HOOK region directly interacts with anionic phospholipids via polybasic and two hydrophobic Phe residues. The β2c-short subunit, which lacks an A domain and contains fewer basic amino acids and no Phe residues in the B domain, neither associates with phospholipids nor affects channel gating dynamically. Together, our data suggest that the flexible HOOK region of the β subunit acts as an important regulator of CaV channel gating via dynamic electrostatic and hydrophobic interaction with the plasma membrane. © 2017 Park et al. -
dc.publisher Rockefeller University Press -
dc.title The HOOK region of voltage-gated Ca2+ channel beta subunits senses and transmits PIP2 signals to the gate -
dc.type Article -
dc.identifier.doi 10.1085/jgp.201611677 -
dc.identifier.scopusid 2-s2.0-85012941633 -
dc.identifier.bibliographicCitation Journal of General Physiology, v.149, no.2, pp.261 - 276 -
dc.subject.keywordPlus Binding -
dc.subject.keywordPlus Calcium Channel -
dc.subject.keywordPlus Domain -
dc.subject.keywordPlus Functional Properties -
dc.subject.keywordPlus Identification -
dc.subject.keywordPlus Inactivation -
dc.subject.keywordPlus Palmitoylation -
dc.subject.keywordPlus Phosphatase -
dc.subject.keywordPlus Phosphoinositides -
dc.subject.keywordPlus Plasma Membrane -
dc.citation.endPage 276 -
dc.citation.number 2 -
dc.citation.startPage 261 -
dc.citation.title Journal of General Physiology -
dc.citation.volume 149 -
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Department of Brain Sciences Laboratory of Brain Signal and Synapse Research 1. Journal Articles

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