期刊
EMBO JOURNAL
卷 20, 期 7, 页码 1674-1680出版社
WILEY
DOI: 10.1093/emboj/20.7.1674
关键词
calcium; calcium signaling; inositol 1,4,5-trisphosphate; IP3 receptor; point mutation
资金
- NINDS NIH HHS [R01 NS38082, R01 NS038082] Funding Source: Medline
Many important cell functions are controlled by Ca2+ release from intracellular stores via the inositol 1,4,5-trisphosphate receptor (IP3R), which requires both IP3 and Ca2+ for its activity. Due to the Ca2+ requirement, the IP3R and the cytoplasmic Ca2+ concentration form a positive feedback loop, which has been assumed to confer regenerativity on the IP3-induced Ca2+ release and to play an important role in the generation of spatiotemporal patterns of Ca2+ signals such as Ca2+ waves and oscillations. Here we show that glutamate 2100 of rat type 1 IP3R (IP(3)R1) is a key residue for the Ca2+ requirement. Substitution of this residue by aspartate (E2100D) results in a 10-fold decrease in the Ca2+ sensitivity without other effects on the properties of the IP3R1. Agonist-induced Ca2+ responses are greatly diminished in cells expressing the E2100D mutant IP(3)R1, particularly the rate of rise of initial Ca2+ spike is markedly reduced and the subsequent Ca2+ oscillations are abolished, These results demonstrate that the Ca2+ sensitivity of the IP3R is functionally indispensable for the determination of Ca2+ signaling patterns.
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