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

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.