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Regulation of InsP3 receptor activity by neuronal Ca2+-binding proteins

Kasri, Nael Nadif; Holmes, Anthony M.; Bultynck, Geert; Parys, Jan B.; Bootman, Martin; Rietdorf, Katja; Missiaen, Ludwig; McDonald, Fraser; De Smedt, Humbert; Conway, Stuart J.; Holmes, Andrew B.; Berridge, Michael J. and Roderick, H. Llewelyn (2004). Regulation of InsP3 receptor activity by neuronal Ca2+-binding proteins. The EMBO Journal, 23(2) pp. 312–21.

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Inositol 1,4,5-trisphosphate receptors (InsP(3)Rs) were recently demonstrated to be activated independently of InsP(3) by a family of calmodulin (CaM)-like neuronal Ca(2+)-binding proteins (CaBPs). We investigated the interaction of both naturally occurring long and short CaBP1 isoforms with InsP(3)Rs, and their functional effects on InsP(3)R-evoked Ca(2+) signals. Using several experimental paradigms, including transient expression in COS cells, acute injection of recombinant protein into Xenopus oocytes and (45)Ca(2+) flux from permeabilised COS cells, we demonstrated that CaBPs decrease the sensitivity of InsP(3)-induced Ca(2+) release (IICR). In addition, we found a Ca(2+)-independent interaction between CaBP1 and the NH(2)-terminal 159 amino acids of the type 1 InsP(3)R. This interaction resulted in decreased InsP(3) binding to the receptor reminiscent of that observed for CaM. Unlike CaM, however, CaBPs do not inhibit ryanodine receptors, have a higher affinity for InsP(3)Rs and more potently inhibited IICR. We also show that phosphorylation of CaBP1 at a casein kinase 2 consensus site regulates its inhibition of IICR. Our data suggest that CaBPs are endogenous regulators of InsP(3)Rs tuning the sensitivity of cells to InsP(3).

Item Type: Journal Item
Copyright Holders: 2004 European Molecular Biology Organization
ISSN: 0261-4189
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 34883
Depositing User: Martin Bootman
Date Deposited: 30 Apr 2013 14:41
Last Modified: 15 Dec 2018 05:52
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