Source:http://linkedlifedata.com/resource/pubmed/id/17905723
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2008-2-29
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pubmed:abstractText |
STIM1 and CRACM1 (or Orai1) are essential molecular components mediating store-operated Ca2+ entry (SOCE) and Ca2+ release-activated Ca2+ (CRAC) currents. Although STIM1 acts as a luminal Ca2+ sensor in the endoplasmic reticulum (ER), the function of STIM2 remains unclear. Here we reveal that STIM2 has two distinct modes of activating CRAC channels: a store-operated mode that is activated through depletion of ER Ca2+ stores by inositol 1,4,5-trisphosphate (InsP3) and store-independent activation that is mediated by cell dialysis during whole-cell perfusion. Both modes are regulated by calmodulin (CaM). The store-operated mode is transient in intact cells, possibly reflecting recruitment of CaM, whereas loss of CaM in perfused cells accounts for the persistence of the store-independent mode. The inhibition by CaM can be reversed by 2-aminoethoxydiphenyl borate (2-APB), resulting in rapid, store-independent activation of CRAC channels. The aminoglycoside antibiotic G418 is a highly specific and potent inhibitor of STIM2-dependent CRAC channel activation. The results reveal a novel bimodal control of CRAC channels by STIM2, the store dependence and CaM regulation, which indicates that the STIM2/CRACM1 complex may be under the control of both luminal and cytoplasmic Ca2+ levels.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ORAI1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/STIM2 protein, human
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1530-6860
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
752-61
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pubmed:dateRevised |
2008-5-14
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pubmed:meshHeading |
pubmed-meshheading:17905723-Calcium,
pubmed-meshheading:17905723-Calcium Channels,
pubmed-meshheading:17905723-Calmodulin,
pubmed-meshheading:17905723-Cell Adhesion Molecules,
pubmed-meshheading:17905723-Cell Line,
pubmed-meshheading:17905723-Cytoplasm,
pubmed-meshheading:17905723-Humans,
pubmed-meshheading:17905723-Membrane Proteins,
pubmed-meshheading:17905723-Up-Regulation
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pubmed:year |
2008
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pubmed:articleTitle |
STIM2 protein mediates distinct store-dependent and store-independent modes of CRAC channel activation.
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pubmed:affiliation |
Center for Biomedical Research and John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii 96813, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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