期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 106, 期 46, 页码 19623-19628出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0907714106
关键词
heteromer; SOC
资金
- Austrian Science Foundation (FWF)
- Austrian Academy of Sciences
- Hertha- Firnberg scholarship holder [T442]
- Austrian Science Fund [P18280, P21118]
- Subproject 11 [W1201]
- Austrian Science Fund (FWF) [T442, P21118, P18280] Funding Source: Austrian Science Fund (FWF)
A general cellular response following depletion of intracellular calcium stores involves activation of store-operated channels (SOCs). While Orai1 forms the native Ca2+ release-activated Ca2+ (CRAC) channel in mast and T cells, the molecular architecture of less Ca2+ selective SOCs is insufficiently defined. Herewepresent evidence that diminished Ca2+ selectivity and robust Cs+ permeation together with a reduced fast inactivation are characteristics of heteromeric Orai1 and Orai3 channels in contrast to their homomeric forms. The first extracellular loop of these Orai isoforms differs by two aspartates replacing glutamates that affect the selectivity. Co-expression of an Orai3 mutant that mimicked the first loop of Orai1 with either Orai1 or Orai3 recovered or decreased Ca2+ selectivity, respectively. Heteromeric Orai1/3 protein assembly provides a concept for less Ca2+ selective SOCs.
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