| Title: |
Regulation of InsP3 receptor activity by neuronal Ca2+-binding proteins. |
| Authors: |
Kasri, N; Holmes, A; Bultynck, G; Parys, J; Bootman, MD; Rietdorf, K; Missiaen, L; McDonald, F; De Smedt, H; Conway, S; Holmes, AB; Berridge, M; Roderick, H |
| Publication Year: |
2016 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
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). |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1038/sj.emboj.7600037 |
| DOI: |
10.1038/sj.emboj.7600037 |
| Availability: |
https://doi.org/10.1038/sj.emboj.7600037; https://ora.ox.ac.uk/objects/uuid:20255752-2a94-4216-ae19-4fc8bb208f82 |
| Rights: |
info:eu-repo/semantics/embargoedAccess |
| Accession Number: |
edsbas.75436AC8 |
| Database: |
BASE |