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Voltage-Gated Calcium Channel Auxiliary β Subunits

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Voltage-Gated Calcium Channels

Abstract

High-voltage-activated Ca2+ channels (HVACCs) convert information encoded in action potentials into Ca2+ fluxes that control critical biological processes, such as muscle contraction, neurotransmitter or hormone release, and regulation of gene expression. HVACCs are hetero-multimeric proteins comprised minimally of a pore-forming α1 subunit assembled with auxiliary cytosolic β and extracellular α2δ subunits. There are four distinct β subunit isoforms with multiple splice variants that are differentially expressed in different tissues and which exhibit some overlap** as well as unique physiological functions. The different CaVβs share a conserved central src homology 3 (SH3) and catalytically inactive guanylate kinase (GK) domain as well as variable N- and C-termini, and middle HOOK region. The conserved SH3-GK module is shared in common with the membrane-associated guanylate kinase (MAGUK) family of scaffold proteins that organize intracellular signaling pathways. CaVβs are important for surface trafficking of pore-forming α1 subunits, and also regulate distinct aspects of channel gating. Some intracellular proteins, such as RGK proteins and Rab3-interacting molecule (RIM), regulate HVACCs via interacting with CaVβ subunits. CaVβ dysregulation is associated with human diseases, and they have been targeted with small molecules as well as engineered proteins to develop HVACC inhibitors.

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Acknowledgments

This work was supported by NIH grants R01 HL121253 and R01 HL122421 (to H.M.C.) and an American Heart Association predoctoral fellowship award (S.B.).

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  1. Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA

    Sergej Borowik & Henry M. Colecraft

  2. Department of Molecular Pharmacology and Therapeutics, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA

    Henry M. Colecraft

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Correspondence to Henry M. Colecraft .

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  1. Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada

    Gerald Werner Zamponi

  2. Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic

    Norbert Weiss

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Borowik, S., Colecraft, H.M. (2022). Voltage-Gated Calcium Channel Auxiliary β Subunits. In: Zamponi, G.W., Weiss, N. (eds) Voltage-Gated Calcium Channels . Springer, Cham. https://doi.org/10.1007/978-3-031-08881-0_4

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