Multiplicity of protein interactions and functions of the voltage-gated calcium channel beta-subunit.
For a long time the auxiliary beta-subunit of voltage-gated calcium channels was thought to be engaged exclusively in the regulation of calcium channel function, including gating, intracellular trafficking, assembly and membrane expression. The beta-subunit belongs to the membrane-associated guanylate kinase class of scaffolding proteins (MAGUK) that comprises a series of protein interaction motifs. Two such domains, a Src homology 3 and a guanylate kinase domain are present in the beta-subunit. Recently, it was shown that this subunit interacts with a variety of proteins and regulates diverse cellular processes ranging from gene expression to hormone secretion and endocytosis. In light of these new findings, the beta-subunit deserves to be promoted to the category of multifunctional regulatory protein. Some of these new functions support a tighter regulation of calcium influx through voltage-gated calcium channels and others apparently serve channel unrelated processes. Here we discuss a variety of protein-protein interactions held by the beta-subunit of voltage-gated calcium channels and their functional consequences. Certainly the identification of additional binding partners and effector pathways will help to understand how the different beta-subunit-mediated processes are interwoven.
Hidalgo
Patricia
P
Institut für Neurophysiologie, Medizinische Hochschule Hannover, 30625 Hannover, Germany. hidalgo.patricia@mh-hannover.de
Neely
Alan
A
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism / Q000502:physiology
D015220:Calcium Channels; D002868:Chromosomal Proteins, Non-Histone; D021122:Protein Subunits; D000090266:Chromobox Protein Homolog 5; D020559:Monomeric GTP-Binding Proteins; D034281:Dynamins; D002118:Calcium