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 beta subunits in assembly and gating of voltage-gated Ca(2+) channels. Here, we report that zygotic deficiency of zebrafish beta4 protein blocks initiation of epiboly, the first morphogenetic movement of teleost embryos. Reduced beta4 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 beta4 cRNA or, surprisingly, by mutant cRNA encoding beta4 subunits incapable of binding to Ca(2+) channel alpha1 subunits. This study defines a YSL-driven zygotic mechanism essential for epiboly initiation and reveals a Ca(2+) channel-independent beta4 protein function potentially involving the cytoskeleton.
Ebert
A M
AM
Department of Biology, Colorado State University, Fort Collins, CO 80523, USA.
McAnelly
C A
CA
Srinivasan
A
A
Linker
J L
JL
Horne
W A
WA
Garrity
D M
DM
D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D004594:Electrophysiology; D005786:Gene Expression Regulation; D006801:Humans; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D015739:Nocodazole / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D050257:Tubulin Modulators / Q000494:pharmacology; D014982:Xenopus laevis; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D050257:Tubulin Modulators; D029961:Zebrafish Proteins; C526206:cacnb4a protein, zebrafish; D015739:Nocodazole