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Title: Regulation of InsP3 receptor activity by neuronal Ca2+-binding proteins
Authors: Nadif Kasri, Nael
Holmes, Anthony M
Bultynck, Geert
Parys, Jan
Bootman, Martin D
Rietdorf, Katja
Missiaen, Ludwig
McDonald, Fraser
De Smedt, Humbert
Conway, Stuart J
Holmes, Andrew B
Berridge, Michael J
Roderick, H Llewelyn # ×
Issue Date: Jan-2004
Series Title: The EMBO journal. vol:23 issue:2 pages:312-21
Abstract: 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).
URI: 
ISSN: 0261-4189
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Physiology Section (-)
Laboratory of Molecular and Cellular Signaling
Experimental Cardiology
× corresponding author
# (joint) last author

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