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内质网在钙库操纵性钙内流过程中的重构。

Remodelling of the endoplasmic reticulum during store-operated calcium entry.

机构信息

Department of Cell Physiology and Metabolism, University of Geneva, 1 rue Michel-Servet CH-1211 Geneva 4, Switzerland.

出版信息

Biol Cell. 2011 Aug;103(8):365-80. doi: 10.1042/BC20100152.

DOI:10.1042/BC20100152
PMID:21736554
Abstract

SOCE (store-operated calcium entry) is a ubiquitous cellular mechanism linking the calcium depletion of the ER (endoplasmic reticulum) to the activation of PM (plasma membrane) Ca2+-permeable channels. The activation of SOCE channels favours the entry of extracellular Ca2+ into the cytosol, thereby promoting the refilling of the depleted ER Ca2+ stores as well as the generation of long-lasting calcium signals. The molecules that govern SOCE activation comprise ER Ca2+ sensors [STIM1 (stromal interaction molecule 1) and STIM2], PM Ca2+-permeable channels {Orai and TRPC [TRP (transient receptor potential) canonical]} and regulatory Ca2+-sensitive cytosolic proteins {CRACR2 [CRAC (Ca2+ release-activated Ca2+ current) regulator 2]}. Upon Ca2+ depletion of the ER, STIM molecules move towards the PM to bind and activate Orai or TRPC channels, initiating calcium entry and store refilling. This molecular rearrangement is accompanied by the formation of specialized compartments derived from the ER, the pre-cER (cortical ER) and cER. The pre-cER appears on the electron microscope as thin ER tubules enriched in STIM1 that extend along microtubules and that are devoid of contacts with the PM. The cER is located in immediate proximity to the PM and comprises thinner sections enriched in STIM1 and devoid of chaperones that might be dedicated to calcium signalling. Here, we review the molecular interactions and the morphological changes in ER structure that occur during the SOCE process.

摘要

SOCE(储存操作钙进入)是一种普遍存在的细胞机制,将内质网(ER)钙耗竭与质膜(PM)钙通透性通道的激活联系起来。SOCE 通道的激活有利于细胞外 Ca2+进入细胞质,从而促进耗尽的 ER Ca2+库的再填充以及产生持久的钙信号。调节 SOCE 激活的分子包括 ER Ca2+传感器[STIM1(基质相互作用分子 1)和 STIM2]、PM 钙通透性通道{Orai 和 TRPC[TRP(瞬时受体电位)经典]}和调节 Ca2+敏感的细胞质蛋白{CRACR2[CRAC(Ca2+释放激活的 Ca2+电流)调节剂 2]}。在 ER 钙耗竭后,STIM 分子向 PM 移动以结合和激活 Orai 或 TRPC 通道,启动钙内流和库再填充。这种分子重排伴随着 ER 衍生的专门隔室的形成,即前 ER(皮质 ER)和 cER。在电子显微镜下,pre-cER 表现为富含 STIM1 的薄 ER 小管,这些小管沿微管延伸,并且与 PM 没有接触。cER 位于与 PM 紧邻的位置,包含较薄的部分,富含 STIM1 且缺乏可能专门用于钙信号的伴侣蛋白。在这里,我们回顾了在 SOCE 过程中发生的 ER 结构的分子相互作用和形态变化。

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