Document Detail

CEP290 interacts with the centriolar satellite component PCM-1 and is required for Rab8 localization to the primary cilium.
MedLine Citation:
PMID:  18772192     Owner:  NLM     Status:  MEDLINE    
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.
Joon Kim; Suguna Rani Krishnaswami; Joseph G Gleeson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-09-04
Journal Detail:
Title:  Human molecular genetics     Volume:  17     ISSN:  1460-2083     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-10     Completed Date:  2008-12-29     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  3796-805     Citation Subset:  IM    
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MeSH Terms
Antigens, Neoplasm / genetics,  metabolism*
Autoantigens / genetics,  metabolism*
Brain Diseases / genetics,  metabolism*
Cell Cycle Proteins / genetics,  metabolism*
Cell Line
Centrioles / genetics,  metabolism*
Cilia / genetics,  metabolism*
Neoplasm Proteins / genetics,  metabolism*
Protein Binding
Protein Transport
rab GTP-Binding Proteins / genetics,  metabolism*
Grant Support
P30 NS047101/NS/NINDS NIH HHS; R01 NS052455/NS/NINDS NIH HHS; R01 NS052455/NS/NINDS NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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