Ca2+ channel-independent requirement for MAGUK family CACNB4 genes in initiation of zebrafish epiboly

CACNB genes encode membrane-associated guanylate kinase (MAGUK) proteins once thought to function exclusively as auxiliary P subunits in assembly and gating of voltage-gated Ca2+ channels. Here, we report that zygotic deficiency of zebrafish beta 4 protein blocks initiation of epiboly, the first morphogenetic movement of teleost embryos. Reduced 134 function in the yolk syncytial layer (YSL) leads to abnormal division and dispersal of yolk syncytial nuclei, blastoderm retraction, and death, effects highly similar to microtubule disruption by nocodazole. Epiboly is restored by coinjection of human 134 cRNA or, surprisingly, by mutant cRNA encoding 134 subunits incapable of binding to Ca2+ channel alpha 1 subunits. This study defines a YSL-driven zygotic mechanism essential for epiboly initiation and reveals a Ca2+ channel-independent beta 4 protein function potentially involving the cytoskeleton.