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

D. Epting, K. Slanchev, C. Boehlke, S. Hoff, N. Loges, T. Yasunaga, L. Indorf, S. Nestel, S. Lienkamp, H. Omran, W. Kuehn, Olaf Ronneberger, G. Walz, a. Kramer-Zucker
Development, 142(1): 174--184, Jan 2015

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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 deuterosome-derived basal bodies with the apical plasma membrane, followed by their correct spacing and planar orientation. Here we report a novel role for ELMO/DOCK180, a bipartite guanine nucleotide exchange factor complex for the small GTPase Rac1, and for the membrane-cytoskeletal linker Ezrin, in regulating the process of 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, likely accounting for the observed phenotypes. These results are substantiated by showing a genetic interaction between ELMO and Ezrin. Finally, we provide biochemical evidence for the ELMO/DOCK180/Rac1 complex influencing Ezrin phosphorylation probably serving 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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BibTex references

@Article{Ron15,
  author       = "D.Epting and K.Slanchev and C.Boehlke and S.Hoff and N.Loges and T.Yasunaga and L.Indorf and S.Nestel and S.Lienkamp and H.Omran and W.Kuehn and O.Ronneberger and G.Walz and and A.Kramer-Zucker",
  title        = "The Rac1 regulator ELMO controls basal body migration and docking in  multiciliated cells through interaction with Ezrin",
  journal      = "Development",
  number       = "1",
  volume       = "142",
  pages        = "174--184",
  month        = "Jan",
  year         = "2015",
  url          = "http://lmb.informatik.uni-freiburg.de//Publications/2015/Ron15"
}

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