Cited 6 time in webofscience Cited 6 time in scopus

Dynamic phospholipid interaction of beta 2e subunit regulates the gating of voltage-gated Ca2+ channels

Title
Dynamic phospholipid interaction of beta 2e subunit regulates the gating of voltage-gated Ca2+ channels
Authors
Kim, DI[Kim, Dong-Il]Park, Y[Park, Yongsoo]Jang, DJ[Jang, Deok-Jin]Suh, BC[Suh, Byung-Chang]
DGIST Authors
Kim, DI[Kim, Dong-Il]; Suh, BC[Suh, Byung-Chang]
Issue Date
2015-06
Citation
Journal of General Physiology, 145(6), 529-541
Type
Article
Article Type
Article
ISSN
0022-1295
Abstract
High voltage-activated Ca2+ (CaV) channels are protein complexes containing pore-forming α1 and auxiliary β and α2δ subunits. The subcellular localization and membrane interactions of the β subunits play a crucial role in regulating CaV channel inactivation and its lipid sensitivity. Here, we investigated the effects of membrane phosphoinositide (PI) turnover on CaV2.2 channel function. The β2 isoform β2e associates with the membrane through electrostatic and hydrophobic interactions. Using chimeric β subunits and liposome-binding assays, we determined that interaction between the N-terminal 23 amino acids of β2e and anionic phospholipids was sufficient for β2e membrane targeting. Binding of the β2e subunit N terminus to liposomes was significantly increased by inclusion of 1% phosphatidylinositol 4,5-bisphosphate (PIP2) in the liposomes, suggesting that, in addition to phosphatidylserine, PIs are responsible for β2e targeting to the plasma membrane. Membrane binding of the β2e subunit slowed CaV2.2 current inactivation. When membrane phosphatidylinositol 4-phosphate and PIP2 were depleted by rapamycin-induced translocation of pseudojanin to the membrane, however, channel opening was decreased and fast inactivation of CaV2.2(β2e) currents was enhanced. Activation of the M1 muscarinic receptor elicited transient and reversible translocation of β2e subunits from membrane to cytosol, but not that of β2a or β3, resulting in fast inactivation of CaV2.2 channels with β2e. These results suggest that membrane targeting of the β2e subunit, which is mediated by nonspecific electrostatic insertion, is dynamically regulated by receptor stimulation, and that the reversible association of β2e with membrane PIs results in functional changes in CaV channel gating. The phospholipid- protein interaction observed here provides structural insight into mechanisms of membrane-protein association and the role of phospholipids in ion channel regulation. © 2015 Kim et al.
URI
http://hdl.handle.net/20.500.11750/1570
DOI
10.1085/jgp.201411349
Publisher
Rockefeller University Press
Related Researcher
Files:
There are no files associated with this item.
Collection:
Brain and Cognitive SciencesETC1. Journal Articles


qrcode mendeley

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE