| Title: |
Regulation of InsP 3 receptor activity by neuronal Ca 2+ -binding proteins |
| Authors: |
Kasri, NN; Holmes, AM; Bultynck, G; Parys, JB; Bootman, MD; Rietdorf, K; Missiaen, L; McDonald, F; De Smedt, H; Conway, Stuart John; Holmes, AB; Berridge, MJ; Roderick, HL |
| Source: |
Kasri , NN , Holmes , AM , Bultynck , G , Parys , JB , Bootman , MD , Rietdorf , K , Missiaen , L , McDonald , F , De Smedt , H , Conway , S J , Holmes , AB , Berridge , MJ & Roderick , HL 2004 , ' Regulation of InsP 3 receptor activity by neuronal Ca 2+ -binding proteins ' , EMBO Journal , vol. 23 , no. 2 , pp. 312-321 . https://doi.org/10.1038/sj.emboj.7600037 |
| Publication Year: |
2004 |
| Subject Terms: |
Ca2+; CaBP; InsP(3); signalling; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; BASOPHILIC LEUKEMIA-CELLS; CALCIUM-RELEASE CHANNELS; ENDOPLASMIC-RETICULUM; TRISPHOSPHATE RECEPTORS; PURKINJE NEURONS; CA2+-INDEPENDENT INHIBITION; FUNCTIONAL-PROPERTIES; CA2+ OSCILLATIONS; CYTOSOLIC CA2+ |
| 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 Ca2+-binding proteins (CaBPs). We investigated the interaction of both naturally occurring long and short CaBP1 isoforms with InsP3Rs, and their functional effects on InsP(3)R-evoked Ca2+ signals. Using several experimental paradigms, including transient expression in COS cells, acute injection of recombinant protein into Xenopus oocytes and Ca-45(2+) flux from permeabilised COS cells, we demonstrated that CaBPs decrease the sensitivity of InsP(3)-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 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 |
| DOI: |
10.1038/sj.emboj.7600037 |
| Availability: |
https://research-portal.st-andrews.ac.uk/en/publications/0bb474b1-0efe-44f7-95e9-88d93b5d762a; https://doi.org/10.1038/sj.emboj.7600037; http://www.scopus.com/inward/record.url?scp=1542290670&partnerID=8YFLogxK |
| Rights: |
info:eu-repo/semantics/restrictedAccess |
| Accession Number: |
edsbas.24C910EC |
| Database: |
BASE |