Unknown

Dataset Information

0

Regulation of primary cilia formation by ceramide.


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 gamma-tubulin, the Rho type GTPase cell division cycle 42 (Cdc42), and atypical protein kinase Czeta/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-3beta (GSK-3beta) inhibitor indirubin-3-monoxime, suggesting that regulation of ciliogenesis depends on the inhibition of GSK-3beta 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.

SUBMITTER: Wang G 

PROVIDER: S-EPMC2739757 | BioStudies | 2009-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC3418310 | BioStudies
2008-01-01 | S-EPMC3812674 | BioStudies
2014-01-01 | S-EPMC4038499 | BioStudies
2011-01-01 | S-EPMC3121392 | BioStudies
1000-01-01 | S-EPMC3113769 | BioStudies
2018-01-01 | S-EPMC6122990 | BioStudies
2019-03-11 | GSE112159 | GEO
2019-03-11 | GSE112158 | GEO
2007-01-01 | S-EPMC5323256 | BioStudies
2010-01-01 | S-EPMC2831760 | BioStudies