Osbpl2 deficiency inhibits Rho/ROCK2/p-ERM signaling and impairs actin cytoskeletal regulation in auditory cells
Cheng Zhang1
Qian Yang1
Yajie Lu2
Qinjun Wei2
Rong Zhou3
Guangqian Xing4
Xin Cao2
Zhibin Chen4
Jun Yao5
1.Department of Medical Genetics,School of Basic Medical Sciences,Nanjing Medical University,Nanjing,Jiangsu 211166,China2.Department of Medical Genetics,School of Basic Medical Sciences,Nanjing Medical University,Nanjing,Jiangsu 211166,China;Jiangsu Key Laboratory of Xenotransplantation,Nanjing Medical University,Nanjing,Jiangsu 211166,China3.Department of Physiology,School of Basic Medical Sciences,Nanjing Medical University,Nanjing,Jiangsu 211166,China4.Department of Otolaryngology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu 210029,China5.Department of Medical Genetics,School of Basic Medical Sciences,Nanjing Medical University,Nanjing,Jiangsu 211166,China;Jiangsu Key Laboratory of Xenotransplantation,Nanjing Medical University,Nanjing,Jiangsu 211166,China;Department of Otolaryngology-Head and Neck Surgery,the Affiliated Taizhou People's Hospital of Nanjing Medical University,Taizhou School of Clinical Medicine,Nanjing Medical University,Taizhou,Jiangsu 225300,China
摘要：A mutation in oxysterol-binding protein-like 2(OSBPL2)has been identified as the genetic cause of autosomal dominant nonsyndromic hearing loss(DFNA67,Online Mendelian Inheritance in Man 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-knockout pigs,suggesting that OSBPL2 plays an important role in regulating 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 regulating the actin cytoskeleton in HCs,contributing to a deeper understanding of the pathogenesis of OSBPL2 mutations in DFNA.
机标关键词：rock2cellsactinauditorycytoskeletaldeficiencyimpairsinhibits
分类号：R764.43(耳科学、耳疾病)
论文发表日期：2025-11-30
在线出版日期：2026-01-15（本平台首次上网日期，不代表文献的发表时间）
页数：14( 574-586,前插6-前插10 )
英文信息