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首页> 外文期刊>Nature >An siRNA screen for NFAT activation identifies septins as coordinators of store-operated Ca~(2+) entry
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An siRNA screen for NFAT activation identifies septins as coordinators of store-operated Ca~(2+) entry

机译：用于NFAT激活的siRNA筛选可将Septins识别为存储操作的Ca〜（2+）条目的协调员

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摘要

The Stim1-Orai1 pathway of store-operated Ca~(2+) entry is an essential component of cellular Ca~(2+) signalling1. STIM1 senses depletion of intracellular Ca~(2+) 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 Ca~(2+) channels. Here we use a genome-wide RNA interference screen in HeLa cells to identify filamentous septin proteins as crucial regulators of store-operated Ca~(2+) entry. Septin filaments and phosphatidyiinositol-4,5-bisphosphate (also known as PtdIns(4,5)P_2) 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)P_2 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.
机译：贮藏操作Ca〜（2+）进入的Stim1-Orai1途径是细胞Ca〜（2+）信号传导的重要组成部分。 STIM1响应于生理刺激而感觉到细胞内Ca〜（2+）存储的耗尽，并在内质网内重新定位到质膜结合的连接处，在其中募集并门控打开质膜ORAI1 Ca〜（2+）通道。在这里，我们在HeLa细胞中使用全基因组RNA干扰筛选，以鉴定丝状Septin蛋白是存储操纵性Ca〜（2+）进入的关键调节剂。在形成STIM1-ORAI1簇之前和期间，内质网-质膜交界处的Septin丝和磷脂酰肌醇-4,5-二磷酸（也称为PtdIns（4,5）P_2）局部重排，从而促进STIM1靶向这些交点并促进稳定招募ORAI1。 PtdIns（4,5）P_2重组和有效的STIM1-ORAI1通信需要交界处的Septin重排。已知Septins划定专门的膜区域，例如树突棘，酵母芽和初级纤毛，并在诸如囊泡运输，细胞极性和胞质分裂的细胞过程中充当膜扩散屏障和/或信号传导枢纽。我们的数据表明，septins还组织了在STIM1-ORAI1信号传导中重要的高度定位的质膜结构域，并表明septins可能组织了与其他信号传导过程相关的膜微区。

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  • 来源
    《Nature》 |2013年第7457期|238-242|共5页
  • 作者

    Sonia Sharma; Ariel Quintana; Gregory M. Findlay; Marcel Mettlen; Beate Baust; Mohit Jain; Roland Nilsson; Anjana Rao; Patrick G. Hogan;

  • 作者单位

    La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA,Program in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA;

    La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA,Program in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA;

    Program in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA;

    The Scripps Research Institute, La Jolla, California 92037, USA;

    Program in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA;

    Broad Institute, Cambridge, Massachusetts 02142, USA,Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA;

    Karolinska Institute, Stockholm 17176, Sweden;

    La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA,Program in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA;

    La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA,Program in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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