English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Dynamic phospholipid interaction of β2e subunit regulates the gating of voltage-gated Ca2+ channels.

Kim, D. I., Park, Y., Jang, D. J., & Suh, B. C. (2015). Dynamic phospholipid interaction of β2e subunit regulates the gating of voltage-gated Ca2+ channels. Journal of General Physiology, 145(6), 529-541. doi:10.1085/jgp.201411349.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-A655-D Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-1101-3
Genre: Journal Article

Files

show Files
hide Files
:
2166529.pdf (Publisher version), 3MB
Name:
2166529.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-

Locators

show
hide
Description:
-

Creators

show
hide
 Creators:
Kim, D. I., Author
Park, Y.1, Author              
Jang, D. J., Author
Suh, B. C., Author
Affiliations:
1Department of Neurobiology, MPI for Biophysical Chemistry, Max Planck Society, ou_578595              

Content

show
hide
Free keywords: -
 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.

Details

show
hide
Language(s): eng - English
 Dates: 2015-05-11
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1085/jgp.201411349
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Journal of General Physiology
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 145 (6) Sequence Number: - Start / End Page: 529 - 541 Identifier: -