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Regulation of InsP 3 receptor activity by neuronal Ca 2+ ‐binding proteins
Author(s) -
Kasri Nael Nadif,
Holmes Anthony M,
Bultynck Geert,
Parys Jan B,
Bootman Martin D,
Rietdorf Katja,
Missiaen Ludwig,
McDonald Fraser,
Smedt Humbert De,
Conway Stuart J,
Holmes Andrew B,
Berridge Michael J,
Roderick H Llewelyn
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600037
Subject(s) - library science , computer science
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 .