The Bcl-2 homolog Nrz inhibits binding of IP3 to its receptor to control calcium signaling during zebrafish epiboly
- Authors
- Bonneau, B., Nougarède, A., Prudent, J., Popgeorgiev, N., Peyriéras, N., Rimokh, R., and Gillet, G.
- ID
- ZDB-PUB-140502-8
- Date
- 2014
- Source
- Science signaling 7(312): ra14 (Journal)
- Registered Authors
- Gillet, Germain, Peyriéras, Nadine
- Keywords
- none
- MeSH Terms
-
- Animals
- Base Sequence
- Blotting, Western
- Calcium Signaling/physiology*
- Cell Movement/physiology*
- Computational Biology
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/physiology*
- Fluorescence Resonance Energy Transfer
- Gene Knockdown Techniques
- Genetic Vectors/genetics
- HeLa Cells
- Humans
- Immunoprecipitation
- Inositol 1,4,5-Trisphosphate/metabolism*
- Inositol 1,4,5-Trisphosphate Receptors/metabolism
- Molecular Dynamics Simulation
- Morpholinos/genetics
- Phosphorylation
- Proto-Oncogene Proteins/genetics
- Proto-Oncogene Proteins/metabolism*
- Sequence Alignment
- Statistics, Nonparametric
- Zebrafish/embryology*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 24518293 Full text @ Sci. Signal.
Members of the Bcl-2 protein family regulate mitochondrial membrane permeability and also localize to the endoplasmic reticulum where they control Ca2+ homeostasis by interacting with inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs). In zebrafish, Bcl-2–like 10 (Nrz) is required for Ca2+ signaling during epiboly and gastrulation. We characterized the mechanism by which Nrz controls IP3-mediated Ca2+ release during this process. We showed that Nrz was phosphorylated during early epiboly, and that in embryos in which Nrz was knocked down, reconstitution with Nrz bearing mutations designed to prevent its phosphorylation disrupted cyclic Ca2+ transients and the assembly of the actin-myosin ring and led to epiboly arrest. In cultured cells, wild-type Nrz, but not Nrz with phosphomimetic mutations, interacted with the IP3 binding domain of IP3R1, inhibited binding of IP3 to IP3R1, and prevented histamine-induced increases in cytosolic Ca2+. Collectively, these data suggest that Nrz phosphorylation is necessary for the generation of IP3-mediated Ca2+ transients and the formation of circumferential actin-myosin cables required for epiboly. Thus, in addition to their role in apoptosis, by tightly regulating Ca2+ signaling, Bcl-2 family members participate in the cellular events associated with early vertebrate development, including cytoskeletal dynamics and cell movement.