کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2037685 | 1072332 | 2009 | 15 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: STIM1 Clusters and Activates CRAC Channels via Direct Binding of a Cytosolic Domain to Orai1 STIM1 Clusters and Activates CRAC Channels via Direct Binding of a Cytosolic Domain to Orai1](/preview/png/2037685.png)
SummaryStore-operated Ca2+ channels activated by the depletion of Ca2+ from the endoplasmic reticulum (ER) are a major Ca2+ entry pathway in nonexcitable cells and are essential for T cell activation and adaptive immunity. After store depletion, the ER Ca2+ sensor STIM1 and the CRAC channel protein Orai1 redistribute to ER-plasma membrane (PM) junctions, but the fundamental issue of how STIM1 activates the CRAC channel at these sites is unresolved. Here, we identify a minimal, highly conserved 107-aa CRAC activation domain (CAD) of STIM1 that binds directly to the N and C termini of Orai1 to open the CRAC channel. Purified CAD forms a tetramer that clusters CRAC channels, but analysis of STIM1 mutants reveals that channel clustering is not sufficient for channel activation. These studies establish a molecular mechanism for store-operated Ca2+ entry in which the direct binding of STIM1 to Orai1 drives the accumulation and the activation of CRAC channels at ER-PM junctions.
Journal: - Volume 136, Issue 5, 6 March 2009, Pages 876–890