The role of auxiliary subunits for the functional diversity of voltage-gated calcium channels.
The role of auxiliary subunits for the functional diversity of voltage-gated calcium channels.
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DOI：
10.1002/jcp.24998
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发表时间：
2015-09
影响因子：
5.6
通讯作者：
Flucher BE
中科院分区：
文献类型：
--
作者：
Campiglio M;Flucher BE
电压门控钙通道 (VGCC) 是将膜去极化转化为分泌、收缩或基因调节等细胞功能的唯一机制。 VGCC 由一个成孔 α1 亚基和几个辅助通道亚基组成。这些亚基有多种亚型和剪接变体，从而产生了可能的亚基组合的惊人的分子多样性。人们普遍认为，特定的辅助亚基对通道进行差异性调节，从而有助于 VGCC 的巨大功能多样性。如果辅助亚基可以与预先存在的通道复合物结合和解离，这将允许通道特性的动态调节。然而，大多数辅助亚基调节电流特性非常相似，并且仍然缺乏任何细胞钙通道功能确实由辅助亚基的生理交换调节的证据。在这篇综述中，我们总结了支持通过交换辅助亚基对钙通道功能进行差异调节的现有信息，以及支持辅助亚基替代功能的实验证据。讨论的核心是这样一个概念：在其天然环境中，VGCC 在大分子信号复合物的背景下发挥作用，并且辅助亚基有助于协调这些钙通道信号体中发现的多种蛋白质-蛋白质相互作用。因此，除了假定的电流特性的差异调节之外，辅助亚基的差异亚细胞靶向特性和差异蛋白质-蛋白质相互作用可以解释对其巨大分子多样性的需求。 J.细胞。生理学。 999：00–00，2015 年。© 2015 作者。 《细胞生理学杂志》由 Wiley periodicals, Inc. 出版。J. Cell。生理学。 230：2019–2031，2015。© 2015 Wiley periodicals, Inc.
Voltage-gated calcium channels (VGCCs) represent the sole mechanism to convert membrane depolarization into cellular functions like secretion, contraction, or gene regulation. VGCCs consist of a pore-forming α1 subunit and several auxiliary channel subunits. These subunits come in multiple isoforms and splice-variants giving rise to a stunning molecular diversity of possible subunit combinations. It is generally believed that specific auxiliary subunits differentially regulate the channels and thereby contribute to the great functional diversity of VGCCs. If auxiliary subunits can associate and dissociate from pre-existing channel complexes, this would allow dynamic regulation of channel properties. However, most auxiliary subunits modulate current properties very similarly, and proof that any cellular calcium channel function is indeed modulated by the physiological exchange of auxiliary subunits is still lacking. In this review we summarize available information supporting a differential modulation of calcium channel functions by exchange of auxiliary subunits, as well as experimental evidence in support of alternative functions of the auxiliary subunits. At the heart of the discussion is the concept that, in their native environment, VGCCs function in the context of macromolecular signaling complexes and that the auxiliary subunits help to orchestrate the diverse protein–protein interactions found in these calcium channel signalosomes. Thus, in addition to a putative differential modulation of current properties, differential subcellular targeting properties and differential protein–protein interactions of the auxiliary subunits may explain the need for their vast molecular diversity. J. Cell. Physiol. 999: 00–00, 2015. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. J. Cell. Physiol. 230: 2019–2031, 2015. © 2015 Wiley Periodicals, Inc.