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Development January 1, 2015; 142 (1): 174-84.
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The Rac1 regulator ELMO controls basal body migration and docking in multiciliated cells through interaction with Ezrin.

Epting D , Slanchev K , Boehlke C , Hoff S , Loges NT , Yasunaga T , Indorf L , Nestel S , Lienkamp SS , Omran H , Kuehn EW , Ronneberger O , Walz G , Kramer-Zucker A .

Cilia are microtubule-based organelles that are present on most cells and are required for normal tissue development and function. Defective cilia cause complex syndromes with multiple organ manifestations termed ciliopathies. A crucial step during ciliogenesis in multiciliated cells (MCCs) is the association of future basal bodies with the apical plasma membrane, followed by their correct spacing and planar orientation. Here, we report a novel role for ELMO-DOCK1, which is a bipartite guanine nucleotide exchange factor complex for the small GTPase Rac1, and for the membrane-cytoskeletal linker Ezrin, in regulating centriole/basal body migration, docking and spacing. Downregulation of each component results in ciliopathy-related phenotypes in zebrafish and disrupted ciliogenesis in Xenopus epidermal MCCs. Subcellular analysis revealed a striking impairment of basal body docking and spacing, which is likely to account for the observed phenotypes. These results are substantiated by showing a genetic interaction between elmo1 and ezrin b. Finally, we provide biochemical evidence that the ELMO-DOCK1-Rac1 complex influences Ezrin phosphorylation and thereby probably serves as an important molecular switch. Collectively, we demonstrate that the ELMO-Ezrin complex orchestrates ciliary basal body migration, docking and positioning in vivo.

PubMed ID: 25516973
Article link: Development

Species referenced: Xenopus laevis
Genes referenced: arl13b cep164 dock1 elmo1 elmo2 ezr msn psmd6 rac1 tuba4b tubg1
GO keywords: ciliary basal body organization [+]
Antibodies: Tuba4b Ab4 Tubg1 Ab4 elmo1 Ab1 elmo2 Ab1 msn Ab1
Morpholinos: dock1 MO1 elmo1 MO1 elmo2 MO1 ezr MO1 rac1 MO1

Disease Ontology terms: ciliopathy

Article Images: [+] show captions
References :
Epting, The Rac1 regulator ELMO controls basal body migration and docking in multiciliated cells through interaction with Ezrin. 2015, Pubmed