Fidgetin-like 1 is a ciliogenesis-inhibitory centrosome protein

Abstract

Fidgetin-like 1 (FIGL-1) is a homolog of fidgetin, an AAA protein that was identified as the protein encoded by the gene mutated in fidget mice. Because the phenotypes of fidget mice are reminiscent of the phenotypes of ciliopathy diseases, and because fidgetin has microtubule-severing activity, we hypothesize that these proteins participate in cilia-related processes. Indeed, overexpression of FIGL-1 interfered with ciliogenesis in cultured cells. In particular, overexpressed FIGL-1 strongly accumulated at the centrosome, and, when highly expressed, perturbed the localization of centrosomal proteins such as pericentrin, CP110, and centrin. Using a polyclonal antibody against human FIGL-1, we found that endogenous FIGL-1 localized preferentially around the mother centriole. Consistently, depletion of FIGL-1 by shRNA treatment enhanced ciliogenesis in HEK293T cells. By checking the integrity of the cytoplasmic microtubule network in FIGL-1-overexpressing cells, we found that FIGL-1 probably has microtubule-severing activity, as suggested by its sequence homology with other microtubule-severing proteins. Furthermore, we showed that overexpression of FIGL-1 in zebrafish embryo decreased the length of cilia and perturbed the heart laterality. Taken together, these results demonstrate that FIGL-1 is a new centrosomal protein and inhibits ciliogenesis. These results extend the already long list of centrosomal proteins and provide new insights into the regulation of ciliogenesis.

VPS4 is a dynamic component of the centrosome that regulates centrosome localization of γ-tubulin, centriolar satellite stability and ciliogenesis

“…VPS4 is a member of a family of AAA ATPase proteins that includes the microtubule severing proteins spastin, katanin and fidgetin 39 , which have also been shown to localize to centrosomes and spindle poles 40 – 43 . Disruption of the ESCRT-independent activity of VPS4 at the centrosome echoes phenotypes of disrupting activity of other AAA ATPase family members: a mutation that prevents katanin ATP hydrolysis reduces the volume of γ-tubulin at spindle poles 44 and changes in the expression levels and activity of fidgetin-like 1 affect ciliogenesis and alter the protein composition of the centrosome 45 . The shared evolutionary origins and similarity of the misregulation consequences at the centrosome raise the possibility that, like other members of the family, VPS4 at the centrosome could target microtubules.…”

The Rice AAA-ATPase OsFIGNL1 Is Essential for Male Meiosis

“…Although there may exist essential and conserved function domains among FIGNL1s, molecular and biological functions of the AAA family members may have diverged among different species. For example, Zhao et al (2016) recently found that human FIGNL1 localizes at centrosomes, and is involved in ciliogenesis. Previous reports showed that C. elegans FIGNL1 binds to microtubules and controls mitotic progression in the germ line ( Luke-Glaser et al, 2007 ).…”

Motor axon navigation relies on Fidgetin-like 1–driven microtubule plus end dynamics

“…These MT-severing enzymes belong to the meiotic clade of the ATPases associated with diverse cellular activities (AAA+) superfamily together with their subsequently discovered paralogues, katanin-like 1, katanin-like 2, fidgetin-like 1 (Fignl1), and fidgetin-like 2 ( Hanson and Whiteheart, 2005 ; Yang et al, 2005 ; Roll-Mecak and McNally, 2010 ; Sharp and Ross, 2012 ). Among these paralogues, Fignl1 was shown to bind MTs in vitro and to participate in MT-dependent cellular processes such as mitosis ( Luke-Glaser et al, 2007 ) and ciliogenesis ( Zhao et al, 2016 ). However, its exact mode of action and its role in vertebrate nervous system development remained poorly explored.…”