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The centriolar satellite proteins Cep72 and Cep290 interact and are required for recruitment of BBS proteins to the cilium
Defects in centrosome and cilium function are associated with phenotypically related syndromes called ciliopathies. Centriolar satellites are centrosome-associated structures, defined by the protein PCM1, that are implicated in centrosomal protein trafficking. We identify Cep72 as a PCM1-interacting...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The American Society for Cell Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431927/ https://www.ncbi.nlm.nih.gov/pubmed/22767577 http://dx.doi.org/10.1091/mbc.E12-02-0134 |
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author | Stowe, Timothy R. Wilkinson, Christopher J. Iqbal, Anila Stearns, Tim |
author_facet | Stowe, Timothy R. Wilkinson, Christopher J. Iqbal, Anila Stearns, Tim |
author_sort | Stowe, Timothy R. |
collection | PubMed |
description | Defects in centrosome and cilium function are associated with phenotypically related syndromes called ciliopathies. Centriolar satellites are centrosome-associated structures, defined by the protein PCM1, that are implicated in centrosomal protein trafficking. We identify Cep72 as a PCM1-interacting protein required for recruitment of the ciliopathy-associated protein Cep290 to centriolar satellites. Loss of centriolar satellites by depletion of PCM1 causes relocalization of Cep72 and Cep290 from satellites to the centrosome, suggesting that their association with centriolar satellites normally restricts their centrosomal localization. We identify interactions between PCM1, Cep72, and Cep290 and find that disruption of centriolar satellites by overexpression of Cep72 results in specific aggregation of these proteins and the BBSome component BBS4. During ciliogenesis, BBS4 relocalizes from centriolar satellites to the primary cilium. This relocalization occurs normally in the absence of centriolar satellites (PCM1 depletion) but is impaired by depletion of Cep290 or Cep72, resulting in defective ciliary recruitment of the BBSome subunit BBS8. We propose that Cep290 and Cep72 in centriolar satellites regulate the ciliary localization of BBS4, which in turn affects assembly and recruitment of the BBSome. Finally, we show that loss of centriolar satellites in zebrafish leads to phenotypes consistent with cilium dysfunction and analogous to those observed in human ciliopathies. |
format | Online Article Text |
id | pubmed-3431927 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-34319272012-11-16 The centriolar satellite proteins Cep72 and Cep290 interact and are required for recruitment of BBS proteins to the cilium Stowe, Timothy R. Wilkinson, Christopher J. Iqbal, Anila Stearns, Tim Mol Biol Cell Articles Defects in centrosome and cilium function are associated with phenotypically related syndromes called ciliopathies. Centriolar satellites are centrosome-associated structures, defined by the protein PCM1, that are implicated in centrosomal protein trafficking. We identify Cep72 as a PCM1-interacting protein required for recruitment of the ciliopathy-associated protein Cep290 to centriolar satellites. Loss of centriolar satellites by depletion of PCM1 causes relocalization of Cep72 and Cep290 from satellites to the centrosome, suggesting that their association with centriolar satellites normally restricts their centrosomal localization. We identify interactions between PCM1, Cep72, and Cep290 and find that disruption of centriolar satellites by overexpression of Cep72 results in specific aggregation of these proteins and the BBSome component BBS4. During ciliogenesis, BBS4 relocalizes from centriolar satellites to the primary cilium. This relocalization occurs normally in the absence of centriolar satellites (PCM1 depletion) but is impaired by depletion of Cep290 or Cep72, resulting in defective ciliary recruitment of the BBSome subunit BBS8. We propose that Cep290 and Cep72 in centriolar satellites regulate the ciliary localization of BBS4, which in turn affects assembly and recruitment of the BBSome. Finally, we show that loss of centriolar satellites in zebrafish leads to phenotypes consistent with cilium dysfunction and analogous to those observed in human ciliopathies. The American Society for Cell Biology 2012-09-01 /pmc/articles/PMC3431927/ /pubmed/22767577 http://dx.doi.org/10.1091/mbc.E12-02-0134 Text en © 2012 Stowe 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 Stowe, Timothy R. Wilkinson, Christopher J. Iqbal, Anila Stearns, Tim The centriolar satellite proteins Cep72 and Cep290 interact and are required for recruitment of BBS proteins to the cilium |
title | The centriolar satellite proteins Cep72 and Cep290 interact and are required for recruitment of BBS proteins to the cilium |
title_full | The centriolar satellite proteins Cep72 and Cep290 interact and are required for recruitment of BBS proteins to the cilium |
title_fullStr | The centriolar satellite proteins Cep72 and Cep290 interact and are required for recruitment of BBS proteins to the cilium |
title_full_unstemmed | The centriolar satellite proteins Cep72 and Cep290 interact and are required for recruitment of BBS proteins to the cilium |
title_short | The centriolar satellite proteins Cep72 and Cep290 interact and are required for recruitment of BBS proteins to the cilium |
title_sort | centriolar satellite proteins cep72 and cep290 interact and are required for recruitment of bbs proteins to the cilium |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431927/ https://www.ncbi.nlm.nih.gov/pubmed/22767577 http://dx.doi.org/10.1091/mbc.E12-02-0134 |
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