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Abstract: FR-PO292

Planar Cell Polarity Effector Fuzzy in Actin Regulation and Ciliogenesis

Session Information

Category: Genetic Diseases of the Kidneys

  • 1101 Genetic Diseases of the Kidneys: Cystic


  • Kalot, Rita Kassem, McGill University Faculty of Medicine and Health Sciences, Montreal, Quebec, Canada
  • Babayeva, Sima, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
  • Torban, Elena, McGill University Faculty of Medicine and Health Sciences, Montreal, Quebec, Canada

Ciliopathies are disorders caused by mutations in the genes controlling cilia assembly and function. Clinical characteristics of ciliopathies include multi-organ syndromes or organ-specific anomalies, including small and/or cystic kidneys. Planar cell polarity (PCP) effector proteins are major regulators of ciliogenesis since defects in either Fuzzy, Wdpcp, or Inturned cause abnormal cilia formation and pleiotropic syndromes. In vertebrates, PCP effectors recruit important ciliary proteins to the ciliary base. Our recent data indicate that Fuzzy interacts with p190A (ArhGap35), a RhoA GAP that suppresses actin polymerization at the ciliary base, and recruits it to the base of the primary cilium, indicating a potential role of Fuzzy and other PCP effectors in actin regulation at the base of the cilium. Therefore, we aim to understand the role of PCP effector-mediated actin regulation in ciliogenesis and ciliopathies.


Ciliation in mouse embryonic fibroblasts (MEF) was assessed by immunofluorescence. Fuzzy-p190A interaction was identified by co-immunoprecipitation. Co-localization of Fuzzy and p190A at the basal body was visualized by Immunofluorescence in Fuzzy-/- and control cells. RhoA activity was assessed by Rhotekin G protein-binding domain-eGFP biosensor in mutant and control cells. Cilia rescue experiments were done using RhoA kinase inhibitors in Fuzzy mutant MEFs and mouse kidney explants.


Knockout of Fuzzy drastically reduces cilia formation in MEFs, however, ciliogenesis in the mutant MEFs and embryonic kidney explants was rescued by ROCK inhibitors. Fuzzy recruits p190A to the ciliary base, where the latter likely prevents excessive actin polymerization and promotes ciliogenesis. Indeed, we detected excessive activation of RhoA (regulator of actin polymerization) at the basal body in Fuzzy-/- MEFs and excessive polymerization in the Fuzzy-/- kidney tissues.


Overall, this study has established the link between Fuzzy and major actin regulator p190A during ciliogenesis. This suggests that Fuzzy regulates actin polymerization at the basal body and thereby may control ciliary trafficking. Identifying additional actin-regulating components downstream of PCP effectors at the ciliary base may help identify novel potential drug targets for the treatment of ciliopathies.


  • Government Support – Non-U.S.