Felix Ricardo, Calderón-Rivera Aida, Andrade Arturo
Department of Cell Biology, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), Mexico City, Mexico.
Department of Neuroscience, Brown University, Providence, RI, USA.
Wiley Interdiscip Rev Membr Transp Signal. 2013 Sep 1;2(5):207-220. doi: 10.1002/wmts.93.
Voltage-gated Ca (Ca) channels mediate Ca ions influx into cells in response to depolarization of the plasma membrane. They are responsible for initiation of excitation-contraction and excitation-secretion coupling, and the Ca that enters cells through this pathway is also important in the regulation of protein phosphorylation, gene transcription, and many other intracellular events. Initial electrophysiological studies divided Ca channels into low-voltage-activated (LVA) and high-voltage-activated (HVA) channels. The HVA Ca channels were further subdivided into L, N, P/Q, and R-types which are oligomeric protein complexes composed of an ion-conducting Ca subunit and auxiliary Ca, Ca, and Ca subunits. The functional consequences of the auxiliary subunits include altered functional and pharmacological properties of the channels as well as increased current densities. The latter observation suggests an important role of the auxiliary subunits in membrane trafficking of the Ca subunit. This includes the mechanisms by which Ca channels are targeted to the plasma membrane and to appropriate regions within a given cell. Likewise, the auxiliary subunits seem to participate in the mechanisms that remove Ca channels from the plasma membrane for recycling and/or degradation. Diverse studies have provided important clues to the molecular mechanisms involved in the regulation of Ca channels by the auxiliary subunits, and the roles that these proteins could possibly play in channel targeting and membrane Stabilization.
电压门控钙(Ca)通道介导钙离子在质膜去极化时流入细胞。它们负责启动兴奋-收缩偶联和兴奋-分泌偶联,通过该途径进入细胞的钙离子在调节蛋白质磷酸化、基因转录和许多其他细胞内事件中也很重要。最初的电生理研究将钙通道分为低电压激活(LVA)通道和高电压激活(HVA)通道。HVA钙通道进一步细分为L型、N型、P/Q型和R型,它们是由离子传导性钙亚基以及辅助性钙亚基、钙亚基和钙亚基组成的寡聚蛋白复合物。辅助亚基的功能后果包括通道功能和药理学特性的改变以及电流密度的增加。后一观察结果表明辅助亚基在钙亚基的膜转运中起重要作用。这包括钙通道靶向质膜以及特定细胞内适当区域的机制。同样,辅助亚基似乎参与了将钙通道从质膜上移除以便再循环和/或降解的机制。各种研究为辅助亚基调节钙通道所涉及的分子机制以及这些蛋白质在通道靶向和膜稳定中可能发挥的作用提供了重要线索。