Publication Date:
2010-10-12
Description:
Calcium signals, pivotal in controlling cell function, can be generated by calcium entry channels activated by plasma membrane depolarization or depletion of internal calcium stores. We reveal a regulatory link between these two channel subtypes mediated by the ubiquitous calcium-sensing STIM proteins. STIM1 activation by store depletion or mutational modification strongly suppresses voltage-operated calcium (Ca(V)1.2) channels while activating store-operated Orai channels. Both actions are mediated by the short STIM-Orai activating region (SOAR) of STIM1. STIM1 interacts with Ca(V)1.2 channels and localizes within discrete endoplasmic reticulum/plasma membrane junctions containing both Ca(V)1.2 and Orai1 channels. Hence, STIM1 interacts with and reciprocally controls two major calcium channels hitherto thought to operate independently. Such coordinated control of the widely expressed Ca(V)1.2 and Orai channels has major implications for Ca(2+) signal generation in excitable and nonexcitable cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601900/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601900/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Youjun -- Deng, Xiaoxiang -- Mancarella, Salvatore -- Hendron, Eunan -- Eguchi, Satoru -- Soboloff, Jonathan -- Tang, Xiang D -- Gill, Donald L -- AI058173/AI/NIAID NIH HHS/ -- HL55426/HL/NHLBI NIH HHS/ -- R01 AI058173/AI/NIAID NIH HHS/ -- R01 HL055426/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2010 Oct 1;330(6000):105-9. doi: 10.1126/science.1191086.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Cardiovascular Research Center, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20929813" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Calcium/metabolism
;
Calcium Channels/genetics/*metabolism
;
Calcium Channels, L-Type/*metabolism
;
Calcium Signaling
;
Cell Line
;
Cell Membrane/metabolism
;
Endoplasmic Reticulum/metabolism
;
Humans
;
Membrane Glycoproteins/chemistry/genetics/*metabolism
;
Muscle, Smooth, Vascular/cytology
;
Mutant Proteins/metabolism
;
Myocytes, Smooth Muscle/*metabolism
;
Patch-Clamp Techniques
;
RNA Interference
;
Rats
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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