Ca2+-sensor region of IP3 receptor controls intracellular Ca2+ signaling
AUTOR(ES)
Miyakawa, Tomoya
FONTE
Oxford University Press
RESUMO
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 (IP3R1) 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 IP3R1, 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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=145472Documentos Relacionados
- Phasic characteristic of elementary Ca2+ release sites underlies quantal responses to IP3
- Modeling of the Modulation by Buffers of Ca2+ Release through Clusters of IP3 Receptors
- On the roles of Ca2+ diffusion, Ca2+ buffers, and the endoplasmic reticulum in IP3-induced Ca2+ waves.
- Changes in IP3 and cytosolic Ca2+ in response to sugars and non-sugar sweeteners in transduction of sweet taste in the rat.
- Immunocytochemical evidence for co-expression of Type III IP3 receptor with signaling components of bitter taste transduction