OSBPL2 deficiency inhibits Rho/ROCK2/p-ERM signaling and impairs actin cytoskeletal regulation in auditory cells.

Mutation in oxysterol-binding protein-like 2 ( OSBPL2) has been identified as the genetic cause of autosomal dominant nonsyndromic hearing loss (DFNA67, OMIM No. 616340). However, the pathogenesis of the OSBPL2 mutation in DFNA remains unclear. Our previous work showed that OSBPL2 deficiency impaired cell adhesion in auditory HEI-OC1 cells. In addition, loss of hair cells (HCs) and morphological abnormalities of HC stereocilia were detected in OSBPL2-disrupted pigs, suggesting that OSBPL2 plays an important role in the regulation of the actin cytoskeleton in auditory cells. In the present study, we found that OSBPL2 deficiency inhibited the Rho/ROCK2 signaling pathway and downregulated phosphorylated Ezrin-Radixin-Moesin (p-ERM), resulting in abnormal F-actin morphology in HEI-OC1 cells and stereociliary defects in mouse HCs. The present study demonstrates the underlying mechanism of OSBPL2 in the regulation of the actin cytoskeleton in HCs, which contributes to a deeper understanding of the pathogenesis of OSBPL2 mutations in DFNA.