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The Clustering of Inositol 1,4,5-Trisphosphate (IP(3)) Receptors Is Triggered by IP(3) Binding and Facilitated by Depletion of the Ca(2+) Store.

The Clustering of Inositol 1,4,5-Trisphosphate (IP(3)) Receptors Is Triggered by IP(3) Binding and Facilitated by Depletion of the Ca(2+) Store. Research Abstract Details 

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  • The Clustering of Inositol 1,4,5-Trisphosphate (IP(3)) Receptors Is Triggered by IP(3) Binding and Facilitated by Depletion of the Ca(2+) Store. Abstract Text:

    The inositol 1,4,5-trisphosphate receptors (IP(3)Rs) form clusters following agonist stimulation, but its mechanism remains controversial. In this study, we visualized the clustering of green fluorescent protein (GFP)-tagged type 3 IP(3)R (GFP-IP(3)R3) in cultured living cells using confocal microscopy. Stimulation with ATP evoked GFP-IP(3)R3 clustering not only in cells with replete Ca(2+)-stores but also in cells with depleted Ca(2+) stores. Thapsigargin (ThG) and ionomycin failed to mimic the ATP-induced cluster formation despite the continuous elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)). Application of IP(3) caused GFP-IP(3)R3 clustering in permeabilized cells, and the response was completely inhibited by heparin, a competitive inhibitor of IP(3)R. Experiments using LIBRAv, an IP(3) biosensor, showed that ATP significantly stimulated IP(3) generation even in store-depleted cells. We also found that pretreatment with ThG accelerated or enhanced the ATP-induced clustering in both the presence and absence of extracellular Ca(2+). When permeabilized cells were stimulated with the threshold of IP(3), the GFP-IP(3)R3 clustering clearly occurred in Ca(2+)-free medium but not in Ca(2+)-containing medium. These results strongly support the hypothesis that the agonist-induced clustering of IP(3)R is triggered by IP(3) binding, rather than [Ca(2+)](i) elevation. Although depletion of the Ca(2+) store by itself does not cause the clustering, it may increase the sensitivity of IP(3)R to cluster formation, leading to facilitation of IP(3)-triggered clustering.

    The Clustering of Inositol 1,4,5-Trisphosphate (IP(3)) Receptors Is Triggered by IP(3) Binding and Facilitated by Depletion of the Ca(2+) Store. Publishing Authors By Initials

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    The Clustering of Inositol 1,4,5-Trisphosphate (IP(3)) Receptors Is Triggered by IP(3) Binding and Facilitated by Depletion of the Ca(2+) Store. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: Journal of pharmacological sciences

    VOLUME: 107

    Page Numbers: 138-50

    Journal Abbreviation: J. Pharmacol. Sci.

    ISSN: 1347-8613

    DAY: 5

    MONTH: 06

    YEAR: 2008

    The Clustering of Inositol 1,4,5-Trisphosphate (IP(3)) Receptors Is Triggered by IP(3) Binding and Facilitated by Depletion of the Ca(2+) Store. Information

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    LANGUAGE: eng

    NlmUniqueID: 101167001

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    Grant and Affiliation Information for The Clustering of Inositol 1,4,5-Trisphosphate (IP(3)) Receptors Is Triggered by IP(3) Binding and Facilitated by Depletion of the Ca(2+) Store.

    AFFILIATION: Department of Pharmacology, School of Dentistry, Health Sciences University of Hokkaido, Japan.

    Country: Japan

    Japan Research PublicationJapan Research Publication

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    MEDLINETA: J Pharmacol Sci

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    The Clustering of Inositol 1,4,5-Trisphosphate IP3 Receptors Is Triggered by IP3 Binding and Facilitated by Depletion of the Ca2+ Store Related Publications

     

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