Promotion of row 1-specific tip complex condensates by Gpsm2-Gαi provides insights into row identity of the tallest stereocilia

被引：110

作者：

Shi, Yingdong ^{[1
]}

Lin, Lin ^{[2
]}

Wang, Chao ^{[1
]}

Zhu, Jinwei ^{[2
]}

机构：

[1] Univ Sci & Technol China, Affiliated Hosp USTC 1, Biomed Sci & Hlth Lab Anhui Prov,Div Life Sci & M, Dept Neurol,Minist Educ,Sch Life Sci,Key Lab Cell, Hefei 230027, Peoples R China

[2] Shanghai Jiao Tong Univ, Minist Educ, Bio X Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Shanghai 200240, Peoples R China

来源：

SCIENCE ADVANCES | 2022年 / 8卷 / 23期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

CELL POLARITY; HEARING-LOSS; CROSS-LINKS; ELONGATION; PROTEINS; MUTATION; WHIRLIN; GPSM2; NUMA; LGN;

D O I：

10.1126/sciadv.abn4556

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The mechanosensory stereocilia in hair cells are organized into rows of graded height, a property crucial for auditory perception. Gpsm2-G alpha i-Whirlin-Myo15-Eps8 complex at tips of the tallest stereocilia is proposed to define hair bundle row identity, although the underlying mechanism remains elusive. Here, we find that Gpsm2 could undergo phase separation. Moreover, row 1-specific Gpsm2-G alpha i complex significantly promotes the formation of the five-component tip complex density (5xTCD) condensates. The 5xTCD condensates display much stronger actin-bundling ability than those without Gpsm2-G alpha i, which may provide critical insights into how Gpsm2-G alpha i specifies the tallest stereocilia. A deafness-associated mutation of Gpsm2 leads to impaired formation of the 5xTCD condensates and consequently reduced actin bundling, providing possible clues for etiology of hearing loss in patients with Chudley-McCullough syndrome.

引用

页数：11