Ca2+-sensor region of IP3 receptor controls intracellular Ca2+ signaling

Citation
T. Miyakawa et al., Ca2+-sensor region of IP3 receptor controls intracellular Ca2+ signaling, EMBO J, 20(7), 2001, pp. 1674-1680
Citations number
42
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
EMBO JOURNAL
ISSN journal
0261-4189 → ACNP
Volume
20
Issue
7
Year of publication
2001
Pages
1674 - 1680
Database
ISI
SICI code
0261-4189(20010402)20:7<1674:CROIRC>2.0.ZU;2-T
Abstract
Many important cell functions are controlled by Ca2+ release from intracell ular stores via the inositol 1,4,5-trisphosphate receptor (IP3R), which req uires 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+ rel ease and to play an important role in the generation of spatiotemporal patt erns 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 Ca2requirement. Substitution of this residue by aspartate (E2100D) results in a 10-fold decrease in the Ca2+ sensitivity without other effects on the pro perties of the IP3R1. Agonist-induced Ca2+ responses are greatly diminished in cells expressing the E2100D mutant IP(3)R1, particularly the rate of ri se of initial Ca2+ spike is markedly reduced and the subsequent Ca2+ oscill ations are abolished, These results demonstrate that the Ca2+ sensitivity o f the IP3R is functionally indispensable for the determination of Ca2+ sign aling patterns.