The Rac1 regulator ELMO controls basal body migration and docking in multiciliated cells through interaction with Ezrin
Citations Over TimeTop 10% of 2014 papers
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.
Related Papers
- → Cep164 mediates vesicular docking to the mother centriole during early steps of ciliogenesis(2012)297 cited
- → Centriole/basal body morphogenesis and migration during ciliogenesis in animal cells(2006)262 cited
- → Centriole and basal body formation during ciliogenesis revisited(1991)127 cited
- → Ciliogenesis and ciliary abnormalities(2000)55 cited
- → Production of Basal Bodies in bulk for dense multicilia formation(2016)32 cited