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The Rac1 regulator ELMO controls basal body migration and docking in multiciliated cells through interaction with Ezrin.

Authors
  • Epting, Daniel
  • Slanchev, Krasimir
  • Boehlke, Christopher
  • Hoff, Sylvia
  • Loges, Niki T
  • Yasunaga, Takayuki
  • Indorf, Lara
  • Nestel, Sigrun
  • Lienkamp, Soeren S
  • Omran, Heymut
  • Kuehn, E Wolfgang
  • Ronneberger, Olaf
  • Walz, Gerd
  • Kramer-Zucker, Albrecht
Type
Published Article
Journal
Development
Publisher
The Company of Biologists
Publication Date
Jan 01, 2015
Volume
142
Issue
1
Pages
174–184
Identifiers
DOI: 10.1242/dev.112250
PMID: 25516973
Source
Medline
Keywords
License
Unknown

Abstract

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.

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