Abstract
Dyslexia is a common neurodevelopmental disorder with a strong genetic component. Independent genetic association studies have implicated the KIAA0319 gene in dyslexia, however its function is still unknown.
We developed a cellular knockout model for KIAA0319 in RPE1 cells 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 showed that KIAA0319 depletion reduced the number of podosomes formed by the cells.
Our results suggest an involvement of KIAA0319 in mechanosensing and force regulation and shows for the first time that podosomes exert highly dynamic, piconewton vertical forces in epithelial cells.
