Hidalgo Patricia, Neely Alan
Institut für Neurophysiologie, Medizinische Hochschule Hannover, 30625 Hannover, Germany.
Cell Calcium. 2007 Oct-Nov;42(4-5):389-96. doi: 10.1016/j.ceca.2007.05.009. Epub 2007 Jul 13.
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.
长期以来，电压门控钙通道的辅助β亚基被认为仅参与钙通道功能的调节，包括门控、细胞内运输、组装和膜表达。β亚基属于膜相关鸟苷酸激酶类支架蛋白（MAGUK），该类蛋白包含一系列蛋白质相互作用基序。β亚基中存在两个这样的结构域，即Src同源3结构域和鸟苷酸激酶结构域。最近的研究表明，该亚基可与多种蛋白质相互作用，并调节从基因表达、激素分泌到内吞作用等多种细胞过程。鉴于这些新发现，β亚基理应被提升到多功能调节蛋白的类别。其中一些新功能支持对通过电压门控钙通道的钙内流进行更严格的调节，而其他功能显然与通道无关。在此，我们讨论电压门控钙通道β亚基所形成的多种蛋白质-蛋白质相互作用及其功能后果。当然，鉴定更多的结合伴侣和效应途径将有助于理解不同β亚基介导的过程是如何相互交织的。
