KIAA0319 influences cilia length, cell migration and mechanical cell-substrate interaction

Abstract

Following its association with dyslexia in multiple genetic studies, the KIAA0319 gene has been extensively investigated in different animal models but its function in neurodevelopment remains poorly understood. We developed the first cellular knockout model for KIAA0319 via CRISPR-Cas9n to investigate its role in processes suggested but not confirmed in previous studies, including cilia formation and cell migration. We found that KIAA0319 knockout increased cilia length and accelerated cell migration. Using Elastic Resonator Interference Stress Microscopy (ERISM), we detected an increase in cellular force for the knockout cells that was restored by a rescue experiment. Combining ERISM and immunostaining we show that KIAA0319 depletion reduces the number of podosomes formed by the cells. Our results suggest an involvement of KIAA0319 in cilia biology and force regulation and show for the first time that podosomes exert highly dynamic, piconewton vertical forces in epithelial cells.