title: 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.
authors.affiliation: a Department of Central Laboratory , Shanghai 10th People's Hospital, School of Life Sciences and Technology, Tongji University , Shanghai , China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhao
authors.affiliation: a Department of Central Laboratory , Shanghai 10th People's Hospital, School of Life Sciences and Technology, Tongji University , Shanghai , China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Jin
authors.affiliation: a Department of Central Laboratory , Shanghai 10th People's Hospital, School of Life Sciences and Technology, Tongji University , Shanghai , China.
authors.forename: Mengzhu
authors.initials: M
authors.lastname: Wang
authors.affiliation: a Department of Central Laboratory , Shanghai 10th People's Hospital, School of Life Sciences and Technology, Tongji University , Shanghai , China.
authors.forename: Lili
authors.initials: L
authors.lastname: Sun
authors.affiliation: a Department of Central Laboratory , Shanghai 10th People's Hospital, School of Life Sciences and Technology, Tongji University , Shanghai , China.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Hong
authors.affiliation: a Department of Central Laboratory , Shanghai 10th People's Hospital, School of Life Sciences and Technology, Tongji University , Shanghai , China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cao
authors.affiliation: a Department of Central Laboratory , Shanghai 10th People's Hospital, School of Life Sciences and Technology, Tongji University , Shanghai , China.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Wang
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle; D002502:Centrioles / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins; D008870:Microtubules / Q000378:metabolism; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D038081:Organogenesis; D034622:RNA Interference; D013347:Subcellular Fractions / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D029961:Zebrafish Proteins; D000251:Adenosine Triphosphatases; C000620422:FIGNL1 protein, zebrafish; D000074183:ATPases Associated with Diverse Cellular Activities; C583279:FIGNL1 protein, human
keywords: AAA protein; centrosome; ciliogenesis; fidgetin-like 1; microtubule