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Functional genomic screen for modulators of ciliogenesis and cilium length.

Authors
Kim, J; Lee, JE; Heynen-Genel, S; Suyama, E; Ono, K; Lee, K; Ideker, T; Aza-Blanc, P; Gleeson, JG
Citation
Nature, 464(7291):1048-1051, 2010
Journal Title
Nature
ISSN
0028-08361476-4687
Abstract
Primary cilia are evolutionarily conserved cellular organelles that organize diverse signalling pathways. Defects in the formation or function of primary cilia are associated with a spectrum of human diseases and developmental abnormalities. Genetic screens in model organisms have discovered core machineries of cilium assembly and maintenance. However, regulatory molecules that coordinate the biogenesis of primary cilia with other cellular processes, including cytoskeletal organization, vesicle trafficking and cell-cell adhesion, remain to be identified. Here we report the results of a functional genomic screen using RNA interference (RNAi) to identify human genes involved in ciliogenesis control. The screen identified 36 positive and 13 negative ciliogenesis modulators, which include molecules involved in actin dynamics and vesicle trafficking. Further investigation demonstrated that blocking actin assembly facilitates ciliogenesis by stabilizing the pericentrosomal preciliary compartment (PPC), a previously uncharacterized compact vesiculotubular structure storing transmembrane proteins destined for cilia during the early phase of ciliogenesis. The PPC was labelled by recycling endosome markers. Moreover, knockdown of modulators that are involved in the endocytic recycling pathway affected the formation of the PPC as well as ciliogenesis. Our results uncover a critical regulatory step that couples actin dynamics and endocytic recycling with ciliogenesis, and also provides potential target molecules for future study.
MeSH terms
Actins/metabolismCell LineCilia/drug effects/*genetics/pathology/*physiologyCytochalasin D/pharmacologyEndocytosisHumansRNA InterferenceTumor Suppressor Proteins/genetics/metabolism
DOI
10.1038/nature08895
PMID
20393563
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Journal Papers > School of Medicine / Graduate School of Medicine > Medical Informatics
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