Regulation of primary cilia formation by ceramide

Guanghu Wang, Kannan Krishnamurthy, Erhard Bieberich

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

The primary cilium is an important sensory organelle, the regulation of which is not fully understood. We found that in polarized Madin-Darby Canine Kidney cells, the sphingolipid ceramide is specifically distributed to a cis-Golgi compartment at the base of the primary cilium. This compartment immunostained for the centrosome marker γ-tubulin, the Rho type GTPase cell division cycle 42 (Cdc42), and atypical protein kinase Cζ/λ (aPKC), a kinase activated by ceramide and associated with a polarity protein complex consisting of partitioning defective (Par)6 and Cdc42. Inhibition of ceramide biosynthesis with Fumonisin B1 prevented codistribution of aPKC and Cdc42 in the centrosomal/pericentriolar compartment and severely impaired ciliogenesis. Cilium formation and codistribution of aPKC and Cdc42 were restored by incubation with N-acetyl or N-palmitoyl sphingosine (C2 or C16 ceramide), or the ceramide analog N-oleoyl serinol (S18). Cilium formation was also restored by the glycogen synthase kinase-3β (GSK-3β) inhibitor indirubin-3-monoxime, suggesting that regulation of ciliogenesis depends on the inhibition of GSK-3β by ceramide-activated aPKC. Consistently, inhibition of aPKC with a pseudosubstrate inhibitor prevented restoration of ciliogenesis by C2 ceramide or S18. Our data show for the first time ceramide is required for primary cilium formation.

Original languageEnglish (US)
Pages (from-to)2103-2110
Number of pages8
JournalJournal of Lipid Research
Volume50
Issue number10
DOIs
StatePublished - Nov 2 2009

Keywords

  • Cell polarity
  • Centrosome
  • Golgi
  • Primary cilium
  • Sphingolipids

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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