This Article Full Text Full Text (PDF) Supplement All Versions of this Article: biophysj.106.101691v1 93/3/834    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by He, L.-l. Articles by Yang, J. Search for Related Content PubMed PubMed Citation Articles by He, L.-l. Articles by Yang, J.

Functional Modularity of the ß-Subunit of Voltage-Gated Ca²⁺ Channels

Department of Biological Sciences, Columbia University, New York, New York 10027

Correspondence: Address reprint requests to Jian Yang, Dept. of Biological Sciences, 917 Fairchild Center, MC2462, Columbia University, New York, NY 10027. Tel.: 212-854-6161; Fax: 212-531-0425; E-mail: jy160{at}columbia.edu.

The ß-subunit of voltage-gated Ca²⁺ channels plays a dual role in chaperoning the channels to the plasma membrane and modulating their gating. It contains five distinct modular domains/regions, including the variable N- and C-terminus, a conserved Src homology 3 (SH3) domain, a conserved guanylate kinase (GK) domain, and a connecting variable and flexible HOOK region. Recent crystallographic studies revealed a highly conserved interaction between the GK domain and interaction domain (AID), the high-affinity binding site in the pore-forming ₁ subunit. Here we show that the AID-GK domain interaction is necessary for ß-subunit-stimulated Ca²⁺ channel surface expression and that the GK domain alone can carry out this function. We also examined the role of each region of all four ß-subunit subfamilies in modulating P/Q-type Ca²⁺ channel gating and demonstrate that the ß-subunit functions modularly. Our results support a model that the conserved AID-GK domain interaction anchors the ß-subunit to the ₁ subunit, enabling ₁-ß pair-specific low-affinity interactions involving the N-terminus and the HOOK region, which confer on each of the four ß-subunit subfamilies its distinctive modulatory properties.

This article has been cited by other articles:

				G. Gonzalez-Gutierrez, E. Miranda-Laferte, D. Nothmann, S. Schmidt, A. Neely, and P. Hidalgo The guanylate kinase domain of the {beta}-subunit of voltage-gated calcium channels suffices to modulate gating PNAS, September 16, 2008; 105(37): 14198 - 14203. [Abstract] [Full Text] [PDF]

				A. M. Ebert, C. A. McAnelly, A. Srinivasan, J. L. Linker, W. A. Horne, and D. M. Garrity Ca2+ channel-independent requirement for MAGUK family CACNB4 genes in initiation of zebrafish epiboly PNAS, January 8, 2008; 105(1): 198 - 203. [Abstract] [Full Text] [PDF]