Essential Ca(V)beta modulatory properties are AID-independent
- PMID: 15750602
- DOI: 10.1038/nsmb909
Essential Ca(V)beta modulatory properties are AID-independent
Abstract
Voltage-gated Ca(2+) channel beta (Ca(v)beta) subunits have a highly conserved core consisting of interacting Src homology 3 and guanylate kinase domains, and are postulated to exert their effects through AID, the major interaction site in the pore-forming alpha(1) subunit. This stereotypical interaction does not explain how individual Ca(v)beta subunits modulate alpha(1) subunits differentially. Here we show that AID is neither necessary nor sufficient for critical Ca(v)beta regulatory properties. Complete modulation depends on additional contacts that are exclusive of AID and not revealed in recent crystal structures. These data offer a new context for understanding Ca(v)beta modulation, suggesting that the AID interaction orients the Ca(v)beta core so as to permit additional isoform-specific Ca(v)alpha(1)-Ca(v)beta interactions that underlie the particular regulation seen with each Ca(v)alpha(1)-Ca(v)beta pair, rather than as the main site of regulation.
Similar articles
-
The guanylate kinase domain of the beta-subunit of voltage-gated calcium channels suffices to modulate gating.Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):14198-203. doi: 10.1073/pnas.0806558105. Epub 2008 Sep 5. Proc Natl Acad Sci U S A. 2008. PMID: 18776052 Free PMC article.
-
A CaVbeta SH3/guanylate kinase domain interaction regulates multiple properties of voltage-gated Ca2+ channels.J Gen Physiol. 2005 Oct;126(4):365-77. doi: 10.1085/jgp.200509354. J Gen Physiol. 2005. PMID: 16186563 Free PMC article.
-
The HOOK-domain between the SH3 and the GK domains of Cavbeta subunits contains key determinants controlling calcium channel inactivation.Channels (Austin). 2007 Mar-Apr;1(2):92-101. doi: 10.4161/chan.4145. Epub 2007 Mar 15. Channels (Austin). 2007. PMID: 18690022
-
The ß subunit of voltage-gated Ca2+ channels.Physiol Rev. 2010 Oct;90(4):1461-506. doi: 10.1152/physrev.00057.2009. Physiol Rev. 2010. PMID: 20959621 Free PMC article. Review.
-
Multiplicity of protein interactions and functions of the voltage-gated calcium channel beta-subunit.Cell Calcium. 2007 Oct-Nov;42(4-5):389-96. doi: 10.1016/j.ceca.2007.05.009. Epub 2007 Jul 13. Cell Calcium. 2007. PMID: 17629941 Review.
Cited by
-
Increase of CaV3 channel activity induced by HVA β1b-subunit is not mediated by a physical interaction.BMC Res Notes. 2018 Nov 14;11(1):810. doi: 10.1186/s13104-018-3917-1. BMC Res Notes. 2018. PMID: 30428904 Free PMC article.
-
Molecular determinants of the CaVbeta-induced plasma membrane targeting of the CaV1.2 channel.J Biol Chem. 2010 Jul 23;285(30):22853-63. doi: 10.1074/jbc.M110.111062. Epub 2010 May 17. J Biol Chem. 2010. PMID: 20478999 Free PMC article.
-
Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation.Channels (Austin). 2010 Nov-Dec;4(6):459-74. doi: 10.4161/chan.4.6.12867. Channels (Austin). 2010. PMID: 21139419 Free PMC article. Review.
-
A quartet of leucine residues in the guanylate kinase domain of CaVβ determines the plasma membrane density of the CaV2.3 channel.J Biol Chem. 2012 Sep 21;287(39):32835-47. doi: 10.1074/jbc.M112.387233. Epub 2012 Jul 30. J Biol Chem. 2012. PMID: 22846999 Free PMC article.
-
Functional assessment of three Rem residues identified as critical for interactions with Ca(2+) channel β subunits.Pflugers Arch. 2015 Nov;467(11):2299-306. doi: 10.1007/s00424-015-1700-x. Epub 2015 Mar 15. Pflugers Arch. 2015. PMID: 25771954
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Miscellaneous
