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rdf:type |
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lifeskim:mentions |
umls-concept:C0439799,
umls-concept:C0439851,
umls-concept:C1167622,
umls-concept:C1335879,
umls-concept:C1511625,
umls-concept:C1515877,
umls-concept:C1552596,
umls-concept:C1704332,
umls-concept:C1823405,
umls-concept:C1879547,
umls-concept:C1947931
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pubmed:issue |
5
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pubmed:dateCreated |
2009-3-9
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-11276202,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-11579153,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-12068047,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-15788710,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-15866891,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-16005298,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-16147976,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-16208375,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-16906149,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-16921383,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-16921385,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-16966422,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-16966423,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-16978865,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-17020874,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-17045966,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-17075073,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-17293345,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-17343823,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-17517596,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-17684017,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-17702753,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-18059270,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-18160041,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-18187424,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-18420579,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-18499724,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-18596693,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-18757751,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-18820677,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-18832420,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-19269360,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-2420465,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-7492298,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-7760017,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19249086-7798233
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1097-4172
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
6
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pubmed:volume |
136
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
876-90
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pubmed:dateRevised |
2011-8-1
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pubmed:meshHeading |
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pubmed:year |
2009
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pubmed:articleTitle |
STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1.
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pubmed:affiliation |
Department of Neurobiology, Stanford University School of Medicine, CA 94305, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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