TY - JOUR
T1 - Ceramide regulates atypical PKCζ/λ-mediated cell polarity in primitive ectoderm cells
T2 - A novel function of sphingolipids in morphogenesis
AU - Krishnamurthy, Kannan
AU - Wang, Guanghu
AU - Silva, Jeane
AU - Condie, Brian G.
AU - Bieberich, Erhard
PY - 2007/1/2
Y1 - 2007/1/2
N2 - 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 PKCζ/λ, its interaction with Cdc42, and phosphorylation of GSK-3β, a substrate of PKCζ/λ. Recombinant PKCζ 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 PKCζ/λ regulates primitive ectoderm cell polarity and morphogenesis.
AB - 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 PKCζ/λ, its interaction with Cdc42, and phosphorylation of GSK-3β, a substrate of PKCζ/λ. Recombinant PKCζ 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 PKCζ/λ regulates primitive ectoderm cell polarity and morphogenesis.
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U2 - 10.1074/jbc.M607779200
DO - 10.1074/jbc.M607779200
M3 - Article
C2 - 17105725
AN - SCOPUS:34047248886
VL - 282
SP - 3379
EP - 3390
IS - 5
ER -