Ceramide regulates atypical PKCζ/λ-mediated cell polarity in primitive ectoderm cells: A novel function of sphingolipids in morphogenesis

Kannan Krishnamurthy, Guanghu Wang, Jeane Silva, Brian G. Condie, Erhard Bieberich

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3379-3390
Number of pages12
JournalJournal of Biological Chemistry
Volume282
Issue number5
DOIs
StatePublished - Jan 2 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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