Research ArticleCalcium signaling

The Bcl-2 Homolog Nrz Inhibits Binding of IP3 to Its Receptor to Control Calcium Signaling During Zebrafish Epiboly

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Science Signaling  11 Feb 2014:
Vol. 7, Issue 312, pp. ra14
DOI: 10.1126/scisignal.2004480

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Nrz-IP3 Tug-of-War

During early development of zebrafish, cells migrate over the yolk in a process known as epiboly. Epiboly requires Ca2+-dependent myosin contraction along actin filaments at the leading edge of the migratory epithelium. Growth factors stimulate production of inositol trisphosphate (IP3), which binds to and activates the IP3 receptor, a Ca2+ channel on the endoplasmic reticulum (ER). Bonneau et al. found that the Bcl-2–like protein Nrz was phosphorylated in zebrafish during early epiboly and that replacing endogenous Nrz with a mutant that could not be phosphorylated disrupted normal Ca2+ oscillations, actin assembly at the leading edge, and epiboly progression. In human cultured cells, wild-type Nrz, but not Nrz with phosphomimetic mutations, bound to the IP3 receptor, prevented its interaction with IP3, and blocked Ca2+ release from the ER. Thus, these data suggest that phosphorylation of Nrz during early epiboly enables IP3 to bind to its receptor and promote Ca2+ waves that are important for assembly of the actin-myosin ring required for cell migration.

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