PUBLICATION
Accumulation of RAF-1 kinase inhibitory protein (RKIP) is associated with CEP290-mediated photoreceptor degeneration in ciliopathies
- Authors
- Murga-Zamalloa, C.A., Ghosh, A.K., Patil, S.B., Reed, N.A., Chan, L.S., Davuluri, S., Peranen, J., Hurd, T.W., Rachel, R.A., and Khanna, H.
- ID
- ZDB-PUB-110629-12
- Date
- 2011
- Source
- The Journal of biological chemistry 286(32): 28276-86 (Journal)
- Registered Authors
- Khanna, Hemant
- Keywords
- centrosome, eye, neurodegeneration, neurons, photoreceptors, cep290, cilia, ciliopathies, retina, retinal degeneration
- MeSH Terms
-
- Animals
- Antigens, Neoplasm/genetics
- Antigens, Neoplasm/metabolism*
- Chlorocebus aethiops
- Cilia/genetics
- PubMed
- 21685394 Full text @ J. Biol. Chem.
Abstract
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 seems to be associated with CEP290-mediated photoreceptor degeneration. Further, our results indicate that preventing accumulation of RKIP could potentially ameliorate such degeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping