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Abstract: FR-PO582

The CPLANE Protein Fuzzy Regulates Primary Ciliogenesis Through Actin Remodeling

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Cystic


  • Kalot, Rita Kassem, McGill University Health Centre, Montreal, Quebec, Canada
  • Babayeva, Sima, McGill University Health Centre, Montreal, Quebec, Canada
  • Torban, Elena, McGill University Health Centre, Montreal, Quebec, Canada

Defects in primary cilia cause a set of diseases termed ciliopathies manifesting in developmental defects including cystic/dysplastic kidneys. Mutations in ciliogenesis and planar cell polarity (CPLANE) genes FUZZY, INTURNED, and WDPCP lead to a ciliopathy spectrum with abnormal kidney phenotypes. Although Fuzzy ortholog in D.Melanogaster was identified as a part of the planar cell polarity and actin regulatory pathway, its functions in primary cilia assembly and ciliopathies remain largely unknown. We hypothesize that Fuzzy modulates actin-assembly involved in primary cilia formation.


The interactions between Fuzzy-Flag, p190A RhoGAP and IQGAP1-GFP were assessed by co-Immunoprecipitation. Rhotekin G protein-binding domain-eGFP biosensor in mutant and control mouse embryonic fibroblast (MEF) cells was used to measure RhoA activity. IQGAP1 was knocked down by siRNA in Retinal Pigmented Epithelial cells (RPE-1). Overexpression of Fuzzy-GFP was done by stable transfection in MDCK cells. Immunofluorescence with gamma-tubulin, Arl13b and phalloidin was used for cilia assessment.


We established that Fuzzy interacts with p190A RhoGAP and controls its localization to the basal body. Normally, p190ARhoAGAP localizes to the primary cilia base and inactivates the actin-regulating protein RhoA. However, in Fuzzy mutant cells, RhoA is excessively activated. We also demonstrate that Fuzzy interacts with IQGAP1 – a protein that facilitates the interaction between p190ARhoGAP and RhoA. siRNA-mediated knockdown of IQGAP1 negatively affected ciliogenesis in RPE-1 cells. On the other hand, we show that Fuzzy is involved in regulation of the early stages of ciliogenesis: the overexpression of Fuzzy in MDCK cells triggered earlier cortical actin clearing at the apical membrane and earlier ciliogenesis.


We conclude that Fuzzy regulates the actin cytoskeleton at the primary cilium during the early and later stages of ciliogenesis. Fuzzy recruits p190A RhoGAP to the ciliary base and interacts with IQGAP1 resulting in the inhibition of RhoA and the suppression of excessive actin polymerization at the base of the cilium. Fuzzy is also involved in the process of actin clearing during the early stages of ciliogenesis, but the exact mechanism is yet to be elucidated.


  • Government Support – Non-U.S.