Liquid-Liquid Phase Separation in Hereditary Hearing Loss

被引：0

作者：

Tao, Kefan ^{[1
]}

Zong, Yanjun ^{[1
]}

Liu, Xiaozhou ^{[1
]}

Shi, Xinyu ^{[1
]}

Zhao, Zhengdong ^{[1
]}

Sun, Yu ^{[1
,2
,3
]}

机构：

[1] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Otorhinolaryngol, Wuhan 430022, Peoples R China

[2] Huazhong Univ Sci & Technol, Union Hosp, Inst Otorhinolaryngol, Tongji Med Coll, Wuhan 430022, Peoples R China

[3] Hubei Prov Clin Res Ctr Deafness & Vertigo, Wuhan 430022, Peoples R China

来源：

NEUROSCIENCE BULLETIN | 2025年

基金：

中国国家自然科学基金;

关键词：

Liquid-liquid phase separation; Hereditary hearing loss; Usher syndrome; Ankle link complex; Post-transcriptional modifications; ALZHEIMER-TYPE DEMENTIA; DNA-BINDING DOMAIN; SANT DOMAIN; DEVELOPING-COUNTRIES; ECONOMIC-IMPACT; MYOSIN VIIA; DE-NOVO; PROTEIN; MEMBRANE; COSTS;

D O I：

10.1007/s12264-025-01446-9

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Hearing loss is one of the most prevalent sensory disorders affecting the human nervous system. Liquid-liquid phase separation (LLPS) is a physiological process that facilitates the reversible and dynamic assembly of biomolecular condensates. Increasing evidence suggests that LLPS plays a significant role in the pathogenesis of hereditary hearing loss. Nevertheless, there is a conspicuous lack of systematic investigations exploring the impact of LLPS abnormalities on the etiology of hereditary hearing loss. In this review, we examine the mechanisms by which dysfunctions in LLPS contribute to hereditary hearing loss, specifically focusing on its effects on mechanoelectrical transduction in hair bundles, transcriptional regulation, post-transcriptional modifications, the actin cytoskeleton, ion homeostasis within the inner ear, and energy and redox homeostasis. Furthermore, we evaluate the considerable potential of targeting LLPS as a therapeutic approach for hearing loss and propose innovative perspectives on LLPS that may guide future research initiatives in the field of auditory disorders.

引用

页数：13

共 122 条

[11] Arginines of the RGG box regulate FMRP association with polyribosomes and mRNA [J].

Blackwell, Ernest ;

Zhang, Xing ;

Ceman, Stephanie .

HUMAN MOLECULAR GENETICS, 2010, 19 (07) :1314-1323

[12] The Novel PMCA2 Pump Mutation Tommy Impairs Cytosolic Calcium Clearance in Hair Cells and Links to Deafness in Mice [J].

Bortolozzi, Mario ;

Brini, Marisa ;

Parkinson, Nick ;

Crispino, Giulia ;

Scimemi, Pietro ;

De Siati, Romolo Daniele ;

Di Leva, Francesca ;

Parker, Andrew ;

Ortolano, Saida ;

Arslan, Edoardo ;

Brown, Steve D. ;

Carafoli, Ernesto ;

Mammano, Fabio .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (48) :37693-37703

[13] The SANT domain: a unique histone-tail-binding module? [J].

Boyer, LA ;

Latek, RR ;

Peterson, CL .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2004, 5 (02) :158-163

[14] Essential role for the SANT domain in the functioning of multiple chromatin remodeling enzymes [J].

Boyer, LA ;

Langer, MR ;

Crowley, KA ;

Tan, S ;

Denu, JM ;

Peterson, CL .

MOLECULAR CELL, 2002, 10 (04) :935-942

[15] Usher type 1G protein sans is a critical component of the tip-link complex, a structure controlling actin polymerization in stereocilia [J].

Caberlotto, Elisa ;

Michel, Vincent ;

Foucher, Isabelle ;

Bahloul, Amel ;

Goodyear, Richard J. ;

Pepermans, Elise ;

Michalski, Nicolas ;

Perfettini, Isabelle ;

Alegria-Prevot, Olinda ;

Chardenoux, Sebastien ;

Do Cruzeiro, Marcio ;

Hardelin, Jean-Pierre ;

Richardson, Guy P. ;

Avan, Paul ;

Weil, Dominique ;

Petit, Christine .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (14) :5825-5830

[16] Cisplatin-Induced Ototoxicity: Effects, Mechanisms and Protection Strategies [J].

Callejo, Angela ;

Sedo-Cabezon, Lara ;

Domenech Juan, Ivan ;

Llorens, Jordi .

TOXICS, 2015, 3 (03) :268-293

[17] The spatial distribution pattern of Connexin26 expression in supporting cells and its role in outer hair cell survival [J].

Chen, Sen ;

Xu, Kai ;

Xie, Le ;

Cao, Hai-Yan ;

Wu, Xia ;

Du, An-Na ;

He, Zu-Hong ;

Lin, Xi ;

Sun, Yu ;

Kong, Wei-Jia .

CELL DEATH & DISEASE, 2018, 9

[18] Mechanotransduction is required for establishing and maintaining mature inner hair cells and regulating efferent innervation [J].

Corns, Laura F. ;

Johnson, Stuart L. ;

Roberts, Terri ;

Ranatunga, Kishani M. ;

Hendry, Aenea ;

Ceriani, Federico ;

Safieddine, Saaid ;

Steel, Karen P. ;

Forge, Andy ;

Petit, Christine ;

Furness, David N. ;

Kros, Corne J. ;

Marcotti, Walter .

NATURE COMMUNICATIONS, 2018, 9

[19] Calcium entry into stereocilia drives adaptation of the mechanoelectrical transducer current of mammalian cochlear hair cells [J].

Corns, Laura F. ;

Johnson, Stuart L. ;

Kros, Corne J. ;

Marcotti, Walter .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (41) :14918-14923

[20] Development of Antibody-Based PROTACs for the Degradation of the Cell-Surface Immune Checkpoint Protein PD-L1 [J].

Cotton, Adam D. ;

Nguyen, Duy P. ;

Gramespacher, Josef A. ;

Seiple, Ian B. ;

Wells, James A. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2021, 143 (02) :593-598

← 1 2 3 4 5 6 7 8 9 10 →