细胞Ca2+信号作用是由STIM(间质相互作用分子)蛋白调控的,后者是内质网中的Ca2+传感器,将Ca2+的库存耗尽与胞质膜中“由Ca2+的释放激发的Ca2+ ”(CRAC) 通道的打开联系起来。ORAI蛋白是CRAC通道的细孔亚单元,控制这一通道的打开。在这篇文章中,Sharma等人发表了一项全基因组RNA干涉分析,它设计用来识别由库存操纵的Ca2+进入的必要调控因子。他们发现,Septin家族的细胞支架细丝是这一过程的重要调控因子,通过ORAI1 与 STIM1之间的联系发挥作用。(生物谷Bioon.com)
生物谷推荐英文摘要:
Nature doi:10.1038/nature12229
An siRNA screen for NFAT activation identifies septins as coordinators of store-operated Ca2+ entry
Sonia Sharma,Ariel Quintana,Gregory M. Findlay,Marcel Mettlen, Beate Baust,Mohit Jain,Roland Nilsson,Anjana Rao & Patrick G. Hogan
The STIM1–ORAI1 pathway of store-operated Ca2+ entry is an essential component of cellular Ca2+ signalling. STIM1 senses depletion of intracellular Ca2+ stores in response to physiological stimuli, and relocalizes within the endoplasmic reticulum to plasma-membrane-apposed junctions, where it recruits and gates open plasma membrane ORAI1 Ca2+ channels. Here we use a genome-wide RNA interference screen in HeLa cells to identify filamentous septin proteins as crucial regulators of store-operated Ca2+ entry. Septin filaments and phosphatidylinositol-4,5-bisphosphate (also known as PtdIns(4,5)P2) rearrange locally at endoplasmic reticulum–plasma membrane junctions before and during formation of STIM1–ORAI1 clusters, facilitating STIM1 targeting to these junctions and promoting the stable recruitment of ORAI1. Septin rearrangement at junctions is required for PtdIns(4,5)P2 reorganization and efficient STIM1–ORAI1 communication. Septins are known to demarcate specialized membrane regions such as dendritic spines, the yeast bud and the primary cilium, and to serve as membrane diffusion barriers and/or signalling hubs in cellular processes such as vesicle trafficking, cell polarity and cytokinesis. Our data show that septins also organize the highly localized plasma membrane domains that are important in STIM1–ORAI1 signalling, and indicate that septins may organize membrane microdomains relevant to other signalling processes.