| CEP290 interacts with the centriolar satellite component PCM-1 and is required for Rab8 localization to the primary cilium. | |
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MedLine Citation:
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PMID: 18772192 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Joubert syndrome (JS) is a developmental brain disorder characterized by cerebellar vermis hypoplasia, abnormal eye movement, ataxia and mental retardation. Mutations in CEP290 mutations are responsible for the cerebello-oculo-renal subtype of JS that includes kidney cysts and retinal degeneration, two phenotypes commonly linked to ciliopathies. CEP290 mutations are also associated with Meckel-Gruber syndrome and Bardet-Biedl syndrome (BBS). Here we demonstrate that CEP290 interacts with a centriolar satellite protein PCM-1, which is implicated in BBS4 function. CEP290 binds to PCM-1 and localizes to centriolar satellites in a PCM-1- and microtubule-dependent manner. The depletion of CEP290 disrupts subcellular distribution and protein complex formation of PCM-1. In accord with PCM-1's role in microtubule organization, CEP290 knockdown causes the disorganization of the cytoplasmic microtubule network. Moreover, we show that both CEP290 and PCM-1 are required for ciliogenesis and are involved in the ciliary targeting of Rab8, a small GTPase shown to collaborate with BBS protein complex to promote ciliogenesis. Our results suggest that PCM-1 is a potential mediator that may link CEP290 with BBS proteins in common molecular pathways. |
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Authors:
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Joon Kim; Suguna Rani Krishnaswami; Joseph G Gleeson |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-09-04 |
Journal Detail:
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Title: Human molecular genetics Volume: 17 ISSN: 1460-2083 ISO Abbreviation: Hum. Mol. Genet. Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-11-10 Completed Date: 2008-12-29 Revised Date: 2012-05-04 |
Medline Journal Info:
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Nlm Unique ID: 9208958 Medline TA: Hum Mol Genet Country: England |
Other Details:
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Languages: eng Pagination: 3796-805 Citation Subset: IM |
Affiliation:
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Department of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, Neoplasm
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genetics,
metabolism* Autoantigens / genetics, metabolism* Brain Diseases / genetics, metabolism* Cell Cycle Proteins / genetics, metabolism* Cell Line Centrioles / genetics, metabolism* Cilia / genetics, metabolism* Humans Neoplasm Proteins / genetics, metabolism* Protein Binding Protein Transport rab GTP-Binding Proteins / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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P30 NS047101/NS/NINDS NIH HHS; R01 NS052455/NS/NINDS NIH HHS; R01 NS052455/NS/NINDS NIH HHS; R01 NS052455-01A2/NS/NINDS NIH HHS; R01 NS052455-02/NS/NINDS NIH HHS; R01 NS052455-03/NS/NINDS NIH HHS; R01 NS052455-06/NS/NINDS NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Neoplasm; 0/Autoantigens; 0/Cell Cycle Proteins; 0/Cep290 protein, human; 0/Neoplasm Proteins; 0/PCM1 protein, human; EC 3.6.1.-/rab GTP-Binding Proteins; EC 3.6.1.-./RAB8A protein, human |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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