title: The Bcl-2 homolog Nrz inhibits binding of IP3 to its receptor to control calcium signaling during zebrafish epiboly.
abstract: 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.
authors: 1Université de Lyon, Centre de recherche en cancérologie de Lyon, U1052 INSERM, UMR CNRS 5286, Université Lyon I, Centre Léon Bérard, 28 rue Laennec, 69008 Lyon, France.
authors: Benjamin
authors: B
authors: Bonneau
authors: Adrien
authors: A
authors: Nougarède
authors: Julien
authors: J
authors: Prudent
authors: Nikolay
authors: N
authors: Popgeorgiev
authors: Nadine
authors: N
authors: Peyriéras
authors: Ruth
authors: R
authors: Rimokh
authors: Germain
authors: G
authors: Gillet
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D020013:Calcium Signaling / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D019295:Computational Biology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology*; D031541:Fluorescence Resonance Energy Transfer; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D060172:Morpholinos / Q000235:genetics; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D018709:Statistics, Nonparametric; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D060172:Morpholinos; D011518:Proto-Oncogene Proteins; D029961:Zebrafish Proteins; C514486:bcl2l10 protein, zebrafish; D015544:Inositol 1,4,5-Trisphosphate