The Bcl-2 homolog Nrz inhibits binding of IP3 to its receptor to control calcium signaling during zebrafish epiboly.

TitleThe Bcl-2 homolog Nrz inhibits binding of IP3 to its receptor to control calcium signaling during zebrafish epiboly.
Publication TypeJournal Article
Year of Publication2014
AuthorsBonneau, B, Nougarède, A, Prudent, J, Popgeorgiev, N, Peyriéras, N, Rimokh, R, Gillet, G
JournalSci Signal
Date Published2014 Feb 11
KeywordsAnimals, Base Sequence, Blotting, Western, Calcium Signaling, Cell Movement, Computational Biology, Embryo, Nonmammalian, Fluorescence Resonance Energy Transfer, Gene Knockdown Techniques, Genetic Vectors, HeLa Cells, Humans, Immunoprecipitation, Inositol 1,4,5-Trisphosphate, Inositol 1,4,5-Trisphosphate Receptors, Molecular Dynamics Simulation, Morpholinos, Phosphorylation, Proto-Oncogene Proteins, Sequence Alignment, Statistics, Nonparametric, Zebrafish, Zebrafish Proteins

Members of the Bcl-2 protein family regulate mitochondrial membrane permeability and also localize to the endoplasmic reticulum where they control Ca(2+) homeostasis by interacting with inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs). In zebrafish, Bcl-2-like 10 (Nrz) is required for Ca(2+) signaling during epiboly and gastrulation. We characterized the mechanism by which Nrz controls IP3-mediated Ca(2+) 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 Ca(2+) 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 Ca(2+). Collectively, these data suggest that Nrz phosphorylation is necessary for the generation of IP3-mediated Ca(2+) transients and the formation of circumferential actin-myosin cables required for epiboly. Thus, in addition to their role in apoptosis, by tightly regulating Ca(2+) signaling, Bcl-2 family members participate in the cellular events associated with early vertebrate development, including cytoskeletal dynamics and cell movement.

Alternate JournalSci Signal
Citation Key10.1126/scisignal.2004480
PubMed ID24518293