Structure and Function of the β Subunit of Voltage-gated Ca²⁺ Channels

Overview

Journal Biochim Biophys Acta

Specialties Biochemistry
Biophysics

Date 2012 Sep 18

PMID 22981275

Citations 67

Authors

Zafir Buraei

Jian Yang

Affiliations

Soon will be listed here.

Abstract

The voltage-gated Ca²⁺ channel β subunit (Ca(v)β) is a cytosolic auxiliary subunit that plays an essential role in regulating the surface expression and gating properties of high-voltage activated (HVA) Ca²⁺ channels. It is also crucial for the modulation of HVA Ca²⁺ channels by G proteins, kinases, Ras-related RGK GTPases, and other proteins. There are indications that Ca(v)β may carry out Ca²⁺ channel-independent functions. Ca(v)β knockouts are either non-viable or result in a severe pathophysiology, and mutations in Ca(v)β have been implicated in disease. In this article, we review the structure and various biological functions of Ca(v)β, as well as recent advances. This article is part of a Special Issue entitled: Calcium channels.

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References

Ikeda S . Voltage-dependent modulation of N-type calcium channels by G-protein beta gamma subunits. Nature. 1996; 380(6571):255-8. DOI: 10.1038/380255a0. View

Pragnell M, De Waard M, Mori Y, Tanabe T, Snutch T, Campbell K . Calcium channel beta-subunit binds to a conserved motif in the I-II cytoplasmic linker of the alpha 1-subunit. Nature. 1994; 368(6466):67-70. DOI: 10.1038/368067a0. View

He L, Zhang Y, Chen Y, Yamada Y, Yang J . Functional modularity of the beta-subunit of voltage-gated Ca2+ channels. Biophys J. 2007; 93(3):834-45. PMC: 1913152. DOI: 10.1529/biophysj.106.101691. View

Chen Y, Li M, Zhang Y, He L, Yamada Y, Fitzmaurice A . Structural basis of the alpha1-beta subunit interaction of voltage-gated Ca2+ channels. Nature. 2004; 429(6992):675-80. DOI: 10.1038/nature02641. View

Cohen R, Foell J, Balijepalli R, Shah V, Hell J, Kamp T . Unique modulation of L-type Ca2+ channels by short auxiliary beta1d subunit present in cardiac muscle. Am J Physiol Heart Circ Physiol. 2004; 288(5):H2363-74. DOI: 10.1152/ajpheart.00348.2004. View

Schredelseker J, Dayal A, Schwerte T, Franzini-Armstrong C, Grabner M . Proper restoration of excitation-contraction coupling in the dihydropyridine receptor beta1-null zebrafish relaxed is an exclusive function of the beta1a subunit. J Biol Chem. 2008; 284(2):1242-51. PMC: 2613631. DOI: 10.1074/jbc.M807767200. View

Harry J, Kobrinsky E, Abernethy D, Soldatov N . New short splice variants of the human cardiac Cavbeta2 subunit: redefining the major functional motifs implemented in modulation of the Cav1.2 channel. J Biol Chem. 2004; 279(45):46367-72. DOI: 10.1074/jbc.M409523200. View

Gamper N, Shapiro M . Regulation of ion transport proteins by membrane phosphoinositides. Nat Rev Neurosci. 2007; 8(12):921-34. DOI: 10.1038/nrn2257. View

Tareilus E, Roux M, Qin N, Olcese R, Zhou J, Stefani E . A Xenopus oocyte beta subunit: evidence for a role in the assembly/expression of voltage-gated calcium channels that is separate from its role as a regulatory subunit. Proc Natl Acad Sci U S A. 1997; 94(5):1703-8. PMC: 19980. DOI: 10.1073/pnas.94.5.1703. View

10.

Stotz S, Barr W, McRory J, Chen L, Jarvis S, Zamponi G . Several structural domains contribute to the regulation of N-type calcium channel inactivation by the beta 3 subunit. J Biol Chem. 2003; 279(5):3793-800. DOI: 10.1074/jbc.M308991200. View

11.

Findeisen F, Minor Jr D . Disruption of the IS6-AID linker affects voltage-gated calcium channel inactivation and facilitation. J Gen Physiol. 2009; 133(3):327-43. PMC: 2654080. DOI: 10.1085/jgp.200810143. View

12.

Takahashi M, Seagar M, Jones J, Reber B, Catterall W . Subunit structure of dihydropyridine-sensitive calcium channels from skeletal muscle. Proc Natl Acad Sci U S A. 1987; 84(15):5478-82. PMC: 298881. DOI: 10.1073/pnas.84.15.5478. View

13.

Wakamori M, Mikala G, Mori Y . Auxiliary subunits operate as a molecular switch in determining gating behaviour of the unitary N-type Ca2+ channel current in Xenopus oocytes. J Physiol. 1999; 517 ( Pt 3):659-72. PMC: 2269381. DOI: 10.1111/j.1469-7793.1999.0659s.x. View

14.

Scott V, De Waard M, Liu H, Gurnett C, Venzke D, Lennon V . Beta subunit heterogeneity in N-type Ca2+ channels. J Biol Chem. 1996; 271(6):3207-12. DOI: 10.1074/jbc.271.6.3207. View

15.

Canti C, Bogdanov Y, Dolphin A . Interaction between G proteins and accessory subunits in the regulation of 1B calcium channels in Xenopus oocytes. J Physiol. 2000; 527 Pt 3:419-32. PMC: 2270102. DOI: 10.1111/j.1469-7793.2000.t01-1-00419.x. View

16.

Almagor L, Chomsky-Hecht O, Ben-Mocha A, Hendin-Barak D, Dascal N, Hirsch J . The role of a voltage-dependent Ca2+ channel intracellular linker: a structure-function analysis. J Neurosci. 2012; 32(22):7602-13. PMC: 6703595. DOI: 10.1523/JNEUROSCI.5727-11.2012. View

17.

Fang K, Colecraft H . Mechanism of auxiliary β-subunit-mediated membrane targeting of L-type (Ca(V)1.2) channels. J Physiol. 2011; 589(Pt 18):4437-55. PMC: 3208217. DOI: 10.1113/jphysiol.2011.214247. View

18.

Larson S, Davidson A . The identification of conserved interactions within the SH3 domain by alignment of sequences and structures. Protein Sci. 2001; 9(11):2170-80. PMC: 2144485. DOI: 10.1110/ps.9.11.2170. View

19.

De Waard M, Pragnell M, Campbell K . Ca2+ channel regulation by a conserved beta subunit domain. Neuron. 1994; 13(2):495-503. DOI: 10.1016/0896-6273(94)90363-8. View

20.

Barclay J, Rees M . Mouse models of spike-wave epilepsy. Epilepsia. 1999; 40 Suppl 3:17-22. DOI: 10.1111/j.1528-1157.1999.tb00894.x. View