STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1.
Cell
; 136(5): 876-90, 2009 Mar 06.
Article
em En
| MEDLINE
| ID: mdl-19249086
ABSTRACT
Store-operated Ca(2+) channels activated by the depletion of Ca(2+) from the endoplasmic reticulum (ER) are a major Ca(2+) entry pathway in nonexcitable cells and are essential for T cell activation and adaptive immunity. After store depletion, the ER Ca(2+) 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 Ca(2+) entry in which the direct binding of STIM1 to Orai1 drives the accumulation and the activation of CRAC channels at ER-PM junctions.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Canais de Cálcio
/
Sinalização do Cálcio
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Proteínas de Membrana
/
Proteínas de Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article