PUBLICATION
Fidgetin-like 1 is a ciliogenesis-inhibitory centrosome protein
- Authors
- Zhao, X., Jin, M., Wang, M., Sun, L., Hong, X., Cao, Y., Wang, C.
- ID
- ZDB-PUB-160708-5
- Date
- 2016
- Source
- Cell cycle (Georgetown, Tex.) 15(17): 2367-75 (Journal)
- Registered Authors
- Cao, Ying
- Keywords
- AAA protein, Fidgetin-like 1, centrosome, ciliogenesis, microtubule
- MeSH Terms
-
- Adenosine Triphosphatases/chemistry
- Adenosine Triphosphatases/metabolism*
- Animals
- Cell Cycle
- Centrioles/metabolism
- Centrosome/metabolism*
- Cilia/metabolism*
- Embryo, Nonmammalian/metabolism
- HEK293 Cells
- Humans
- Mice
- Microtubules/metabolism
- NIH 3T3 Cells
- Nuclear Proteins/chemistry
- Nuclear Proteins/metabolism*
- Organogenesis*
- RNA Interference
- Subcellular Fractions/metabolism
- Zebrafish/embryology
- Zebrafish/metabolism
- Zebrafish Proteins/metabolism*
- PubMed
- 27384458 Full text @ Cell Cycle
Citation
Zhao, X., Jin, M., Wang, M., Sun, L., Hong, X., Cao, Y., Wang, C. (2016) Fidgetin-like 1 is a ciliogenesis-inhibitory centrosome protein. Cell cycle (Georgetown, Tex.). 15(17):2367-75.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping