CSN5/Jab1 inhibits cardiac L-type Ca2+ channel activity through protein-protein interactions
CSN5/Jab1 inhibits cardiac L-type Ca2+ channel activity through protein-protein interactions
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DOI：
10.1016/j.yjmcc.2006.01.007
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发表时间：
2006-04-01
影响因子：
5
通讯作者：
Tohse, N
中科院分区：
文献类型：
--
作者：
Kameda, K;Fukao, M;Tohse, N
L型钙通道具有广泛的组织分布，在生理反应中起重要作用。最近的研究表明，L-型Ca ~（2+）通道的调节涉及大分子信号复合物的组装，如β（2）-肾上腺素能受体信号复合物、小G蛋白kir/Gem和BK通道。在这里，我们报告了以前未确定的作用，另一种蛋白质在结合的α（1C）亚基的L-型钙离子通道的II-III接头。该蛋白是COP 9信号体亚基5（CSN 5）/Jun激活结构域结合蛋白1（Jab 1）。我们已经证明，在酵母双杂交系统中，CSN 5与α（1C）亚基的II-III接头特异性相互作用。α（1C）亚基和CSN 5在大鼠心脏共免疫沉淀，这两种蛋白质共定位于心肌细胞的肌膜和横小管。使用siRNA沉默CSN 5 mRNA降低了COS 7细胞中CSN 5的内源性蛋白水平，并激活了COS 7细胞中表达的L型Ca 2+通道。这些数据表明，CSN 5是一种蛋白质，它在与心脏L型钙离子通道的关联中起着新定义的功能作用。(c)2006爱思唯尔有限公司版权所有。
L-type Ca2+ channels have a wide tissue distribution and play essential roles in physiological responses. Recent studies have indicated that regulation of L-type Ca2+ channels involves the assembly of macromolecular signaling complexes such as the beta(2)-adrenergic receptor signaling complex, the small G-protein kir/Gem and the BK channel. Here, we report the previously unidentified role of another protein in binding to the II-III linker of the alpha(1C) subunit of the L-type Ca2+ channel. This protein is COP9 signalosome subunit 5 (CSN5)/Jun activation domain-binding protein 1 (Jab1). We have demonstrated that CSN5 interacts specifically with the II-III linker of the alpha(1C) subunit in a yeast two-hybrid system. The alpha(1C) subunit and CSN5 were coimmunoprecipitated in rat heart and both proteins were colocalized in sarcoleminal membranes and transverse tubules of cardiac myocytes. Silencing of CSN5 mRNA using siRNA decreased the endogenous protein level of CSN5 and activated L-type Ca2+ channels expressed in COS7 cells. These data indicate that CSN5 is a protein that plays a newly defined functional role in association with the cardiac L-type Ca2+ channel. (c) 2006 Elsevier Ltd. All rights reserved.