Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 282, Issue 5, Pages 3379-3390Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M607779200
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- NINDS NIH HHS [R01NS046835] Funding Source: Medline
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In mammals, the primitive ectoderm is an epithelium of polarized cells that differentiates into all embryonic tissues. Our study shows that in primitive ectoderm cells, the sphingolipid ceramide was elevated and co-distributed with the small GTPase Cdc42 and cortical F-actin at the apicolateral cell membrane. Pharmacological or RNA interference-mediated inhibition of ceramide biosynthesis enhanced apoptosis and impaired primitive ectoderm formation in embryoid bodies differentiated from mouse embryonic stem cells. Primitive ectoderm formation was restored by incubation with ceramide or a ceramide analog. Ceramide depletion prevented plasma membrane translocation of PKC zeta/lambda, its interaction with Cdc42, and phosphorylation of GSK-3 beta, a substrate of PKC zeta/lambda. Recombinant PKC zeta formed a complex with the polarity protein Par6 and Cdc42 when bound to ceramide containing lipid vesicles. Our data suggest a novel mechanism by which a ceramide-induced, apicolateral polarity complex with PKC zeta/lambda regulates primitive ectoderm cell polarity and morphogenesis.
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