細(xì)胞Ca2+信號(hào)作用是由STIM（間質(zhì)相互作用分子）蛋白調(diào)控的，后者是內(nèi)質(zhì)網(wǎng)中的Ca2+傳感器,，將Ca2+的庫存耗盡與胞質(zhì)膜中“由Ca2+的釋放激發(fā)的Ca2+ ”(CRAC) 通道的打開聯(lián)系起來,。ORAI蛋白是CRAC通道的細(xì)孔亞單元,，控制這一通道的打開。在這篇文章中,，Sharma等人發(fā)表了一項(xiàng)全基因組RNA干涉分析,，它設(shè)計(jì)用來識(shí)別由庫存操縱的Ca2+進(jìn)入的必要調(diào)控因子。他們發(fā)現(xiàn),，Septin家族的細(xì)胞支架細(xì)絲是這一過程的重要調(diào)控因子,，通過ORAI1 與 STIM1之間的聯(lián)系發(fā)揮作用。（生物谷Bioon.com）
生物谷推薦英文摘要：
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.
