期刊
JOURNAL OF LIPID RESEARCH
卷 50, 期 10, 页码 2103-2110出版社
ELSEVIER
DOI: 10.1194/jlr.M900097-JLR200
关键词
sphingolipids; cell polarity; primary cilium; Golgi; centrosome
资金
- National Institutes of Health [R01NS046835]
- March of Dimes [6-FY08-322]
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 gamma-tubulin, the Rho type GTPase cell division cycle 42 (Cdc42), and atypical protein kinase C zeta/lambda (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-3 beta (GSK3 beta) inhibitor indirubin-3-monoxime, suggesting that regulation of ciliogenesis depends on the inhibition of GSK-3 beta 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 that ceramide is required for primary cilium formation.-Wang, G., K. Krishnamurthy, and E. Bieberich. Regulation of primary cilia formation by ceramide. J. Lipid Res. 2009. 50: 2103-2110.
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