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- Title
Regulation of InsP<sub>3</sub> receptor activity by neuronal Ca<sup>2+</sup>-binding proteins.
- Authors
Kasri, Nael Nadif; Holmes, Anthony M.; Bultynck, Geert; Parys, Jan B.; Bootman, Martin D.; Rietdorf, Katja; Missiaen, Ludwig; McDonald, Fraser; De Smedt, Humbert; Conway, Stuart J.; Holmes, Andrew B.; Berridge, Michael J.; Roderick, H. Llewelyn
- Abstract
Inositol 1,4,5-trisphosphate receptors (InsP3Rs) were recently demonstrated to be activated independently of InsP3 by a family of calmodulin (CaM)-like neuronal Ca2+binding proteins (CaBPs). We investigated the interaction of both naturally occurring long and short CaBP1 isoforms with InsP3Rs, and their functional effects on InsP3Revoked Ca2+ signals. Using several experimental paradigms, including transient expression in COS cells, acute injection of recombinant protein into Xenopus oocytes and 45Ca2+ flux from permeabilised COS cells, we demonstrated that CaBPs decrease the sensitivity of InsP3-induced Ca2+ release (IICR). In addition, we found a Ca2+-independent interaction between CaBP1 and the NH2-terminal 159 amino acids of the type 1 InsP3R. This interaction resulted in decreased InsP3 binding to the receptor reminiscent of that observed for CaM. Unlike CaM, however, CaBPs do not inhibit ryanodine receptors, have a higher affinity for InsP3Rs 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 InsP3Rs tuning the sensitivity of cells to InsP3.
- Subjects
INOSITOL; CARRIER proteins; INOSITOL phosphates; HEXOSE phosphates; CALMODULIN; CALCIUM-binding proteins
- Publication
EMBO Journal, 2004, Vol 23, Issue 2, p312
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1038/sj.emboj.7600037