Actin filament severing protein Wdr1 promotes primary cilia assembly

<title>Abstract</title> <p>Actin cytoskeletal remodeling has emerged as a critical regulator of ciliogenesis. Based on a genome-wide siRNA screen that identified candidate regulators of ciliogenesis, we employed a candidate-based approach to investigate the role of the WD repeat-containing protein Wdr1 in ciliogenesis. Wdr1 potentiates Cofilin-mediated actin filament severing and is frequently mutated in patients with immunological disorders characterized by abnormal F-actin accumulation. Using siRNA-mediated depletion in both human RPE1 and mouse NIH3T3 cells, we demonstrate that Wdr1 is an essential actin cytoskeletal remodeling factor required for efficient ciliogenesis in serum starved cells. The ciliogenesis defect caused by Wdr1 depletion was rescued by pharmacological depolymerization of the excess F-actin or by ectopic expression of an siRNA-resistant wild type Wdr1 construct, but not by expression of the disease-associated Wdr1 mutant, which is predicted to disrupt the structural integrity and function of the protein. Collectively, our findings support a model in which Wdr1 promotes cofilin-dependent actin filament severing and dynamic cytoskeletal remodeling, thereby facilitating centrosome migration toward the apical membrane and efficient primary cilia assembly.</p>