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Characterization of an apical ceramide-enriched compartment regulating ciliogenesis
We show that in Madin–Darby canine kidney (MDCK) cells, an apical ceramide-enriched compartment (ACEC) at the base of primary cilia is colocalized with Rab11a. Ceramide and Rab11a vesicles isolated by magnetic sorting contain a highly similar profile of proteins (atypical protein kinase C [aPKC], Cd...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418310/ https://www.ncbi.nlm.nih.gov/pubmed/22718902 http://dx.doi.org/10.1091/mbc.E12-02-0079 |
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author | He, Qian Wang, Guanghu Dasgupta, Somsankar Dinkins, Michael Zhu, Gu Bieberich, Erhard |
author_facet | He, Qian Wang, Guanghu Dasgupta, Somsankar Dinkins, Michael Zhu, Gu Bieberich, Erhard |
author_sort | He, Qian |
collection | PubMed |
description | We show that in Madin–Darby canine kidney (MDCK) cells, an apical ceramide-enriched compartment (ACEC) at the base of primary cilia is colocalized with Rab11a. Ceramide and Rab11a vesicles isolated by magnetic sorting contain a highly similar profile of proteins (atypical protein kinase C [aPKC], Cdc42, Sec8, Rab11a, and Rab8) and ceramide species, suggesting the presence of a ciliogenic protein complex associated with ceramide at the ACEC. It is intriguing that C16 and C18 ceramide, although less abundant ceramide species in MDCK cells, are highly enriched in ceramide and Rab11a vesicles. Expression of a ceramide-binding but dominant-negative mutant of aPKC suppresses ciliogenesis, indicating that the association of ceramide with aPKC is critical for the formation of this complex. Our results indicate that ciliogenic ceramide is derived from apical sphingomyelin (SM) that is endocytosed and then converted to the ACEC. Consistently, inhibition of acid sphingomyelinase with imipramine disrupts ACEC formation, association of ciliogenic proteins with Rab11a vesicles, and cilium formation. Ciliogenesis is rescued by the histone deacetylase (HDAC) inhibitor trichostatin A, indicating that ceramide promotes tubulin acetylation in cilia. Taken together, our results suggest that the ACEC is a novel compartment in which SM-derived ceramide induces formation of a ciliogenic lipid–protein complex that sustains primary cilia by preventing deacetylation of microtubules. |
format | Online Article Text |
id | pubmed-3418310 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-34183102012-10-30 Characterization of an apical ceramide-enriched compartment regulating ciliogenesis He, Qian Wang, Guanghu Dasgupta, Somsankar Dinkins, Michael Zhu, Gu Bieberich, Erhard Mol Biol Cell Articles We show that in Madin–Darby canine kidney (MDCK) cells, an apical ceramide-enriched compartment (ACEC) at the base of primary cilia is colocalized with Rab11a. Ceramide and Rab11a vesicles isolated by magnetic sorting contain a highly similar profile of proteins (atypical protein kinase C [aPKC], Cdc42, Sec8, Rab11a, and Rab8) and ceramide species, suggesting the presence of a ciliogenic protein complex associated with ceramide at the ACEC. It is intriguing that C16 and C18 ceramide, although less abundant ceramide species in MDCK cells, are highly enriched in ceramide and Rab11a vesicles. Expression of a ceramide-binding but dominant-negative mutant of aPKC suppresses ciliogenesis, indicating that the association of ceramide with aPKC is critical for the formation of this complex. Our results indicate that ciliogenic ceramide is derived from apical sphingomyelin (SM) that is endocytosed and then converted to the ACEC. Consistently, inhibition of acid sphingomyelinase with imipramine disrupts ACEC formation, association of ciliogenic proteins with Rab11a vesicles, and cilium formation. Ciliogenesis is rescued by the histone deacetylase (HDAC) inhibitor trichostatin A, indicating that ceramide promotes tubulin acetylation in cilia. Taken together, our results suggest that the ACEC is a novel compartment in which SM-derived ceramide induces formation of a ciliogenic lipid–protein complex that sustains primary cilia by preventing deacetylation of microtubules. The American Society for Cell Biology 2012-08-15 /pmc/articles/PMC3418310/ /pubmed/22718902 http://dx.doi.org/10.1091/mbc.E12-02-0079 Text en © 2012 He et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles He, Qian Wang, Guanghu Dasgupta, Somsankar Dinkins, Michael Zhu, Gu Bieberich, Erhard Characterization of an apical ceramide-enriched compartment regulating ciliogenesis |
title | Characterization of an apical ceramide-enriched compartment regulating ciliogenesis |
title_full | Characterization of an apical ceramide-enriched compartment regulating ciliogenesis |
title_fullStr | Characterization of an apical ceramide-enriched compartment regulating ciliogenesis |
title_full_unstemmed | Characterization of an apical ceramide-enriched compartment regulating ciliogenesis |
title_short | Characterization of an apical ceramide-enriched compartment regulating ciliogenesis |
title_sort | characterization of an apical ceramide-enriched compartment regulating ciliogenesis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418310/ https://www.ncbi.nlm.nih.gov/pubmed/22718902 http://dx.doi.org/10.1091/mbc.E12-02-0079 |
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