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Fahrner, M; Muik, M; Derler, I; Schindl, R; Fritsch, R; Frischauf, I; Romanin, C.
Mechanistic view on domains mediating STIM1-Orai coupling.
Immunol Rev. 2009; 231(1): 99-112.
Doi: 10.1111/j.1600-065X.2009.00815.x
Web of Science
PubMed
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- Co-authors Med Uni Graz
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Schindl Rainer
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Calcium (Ca2+) entry into non-excitable cells is mainly carried by store-operated channels, which serve essential functions ranging from regulation of transcription to cell growth. The best-characterized store-operated current, initially discovered in T lymphocytes and mast cells, is the Ca2+ release-activated Ca2+ (CRAC) current. The search for the molecular components of the CRAC channel has recently identified stromal interaction molecule 1 (STIM1) as the Ca2+ sensor in the endoplasmic reticulum (ER) and Orai1 as the CRAC channel pore. ER store depletion results in formation of STIM1 puncta that trigger Ca2+ influx via Orai1 channels. This review covers the role of domains within STIM1 and Orai and enlightens their function in the STIM1/Orai coupling process. Moreover, a molecular interpretation focuses on interactions between cytosolic portions of STIM1 and Orai together with a mechanistic view on the loss of function of the SCID (severe combined immunodeficiency)-linked Orai1 R91W mutant channel. The architecture of the selectivity filter of Orai channels is finally elucidated based on permeation properties of Orai pore mutants.
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Animals -
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Calcium - metabolism
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Calcium Channels - chemistry
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Calcium Channels - genetics
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Calcium Channels - metabolism
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Cytosol - metabolism
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Humans -
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Membrane Proteins - chemistry
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Membrane Proteins - genetics
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Membrane Proteins - metabolism
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Protein Binding -
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signal transduction
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signaling proteins
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immunodeficiency diseases
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mast cells
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T cells