Document Detail

Accumulation of the Raf-1 kinase inhibitory protein (Rkip) is associated with Cep290-mediated photoreceptor degeneration in ciliopathies.
MedLine Citation:
PMID:  21685394     Owner:  NLM     Status:  MEDLINE    
Primary cilia regulate polarized protein trafficking in photoreceptors, which are dynamic and highly compartmentalized sensory neurons of retina. The ciliary protein Cep290 modulates cilia formation and is frequently mutated in syndromic and non-syndromic photoreceptor degeneration. However, the underlying mechanism of associated retinopathy is unclear. Using the Cep290 mutant mouse rd16 (retinal degeneration 16), we show that Cep290-mediated photoreceptor degeneration is associated with aberrant accumulation of its novel interacting partner Rkip (Raf-1 kinase inhibitory protein). This effect is phenocopied by morpholino-mediated depletion of cep290 in zebrafish. We further demonstrate that ectopic accumulation of Rkip leads to defective cilia formation in zebrafish and cultured cells, an effect mediated by its interaction with the ciliary GTPase Rab8A. Our data suggest that Rkip prevents cilia formation and is associated with Cep290-mediated photoreceptor degeneration. Furthermore, our results indicate that preventing accumulation of Rkip could potentially ameliorate such degeneration.
Carlos A Murga-Zamalloa; Amiya K Ghosh; Suresh B Patil; Nathan A Reed; Lan Sze Chan; Supriya Davuluri; Johan Peränen; Toby W Hurd; Rivka A Rachel; Hemant Khanna
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-06-17
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-11     Completed Date:  2012-05-11     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  28276-86     Citation Subset:  IM    
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor,Michigan 48105, USA.
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MeSH Terms
Antigens, Neoplasm / genetics,  metabolism*
Cercopithecus aethiops
Cilia / genetics,  metabolism,  pathology
Ciliary Motility Disorders / genetics,  metabolism*,  pathology
HEK293 Cells
Microtubule-Associated Proteins / genetics,  metabolism*
Neoplasm Proteins / genetics,  metabolism*
Nuclear Proteins / genetics,  metabolism*
Phosphatidylethanolamine Binding Protein / genetics,  metabolism*
Retinal Degeneration / genetics,  metabolism*,  pathology
Zebrafish Proteins / genetics,  metabolism*
rab GTP-Binding Proteins / genetics,  metabolism
Grant Support
Reg. No./Substance:
0/Antigens, Neoplasm; 0/Cep290 protein, human; 0/Cep290 protein, mouse; 0/Microtubule-Associated Proteins; 0/Neoplasm Proteins; 0/Nuclear Proteins; 0/PEBP1 protein, human; 0/Phosphatidylethanolamine Binding Protein; 0/Rab8a protein, mouse; 0/Raf kinase inhibitory protein, mouse; 0/Zebrafish Proteins; 0/centrosomal protein 290, zebrafish; EC 3.6.1.-/Rab8a protein, zebrafish; 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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