期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 286, 期 32, 页码 28276-28286出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M111.237560
关键词
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资金
- National Institutes of Health [EY007961, 5P60 DK20572]
- Michigan Diabetes Research and Training Center
- Foundation for Fighting Blindness
- Midwest Eye Banks and Transplantation Center
- Vision Core Facilities [EY07003]
Primary cilia regulate polarized protein trafficking in photo-receptors, 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.
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