PXD076160

PXD076160 is an original dataset announced via ProteomeXchange.

Title	Pathogenic Mechanism of the PLS1 Gene Variant in Hearing Loss and Functional Validation in a Zebrafish Model
Description	PLS1, encoding an actin-bundling protein Plastin 1, is one of the pathogenic genes responsible for autosomal dominant non-syndromic hearing loss. The cellular damage caused by mutant plastin proteins may arise from loss of function and/or dominant-negative effects. In this study, we investigated the pathogenic mechanism of PLS1 mutations by establishing both in vitro cellular models and in vivo zebrafish models. Immunoprecipitation demonstrated that the ΔExon8 mutation disrupts the intramolecular interaction between the ABD1 and ABD2 domains, while immunofluorescence colocalization revealed that the mutation alters the binding pattern of PLS1 to actin bundles and disturbs cytoskeletal organization. Through zebrafish FM1-43 uptake assays, we showed that the mutant protein impaired the functional opening and permeability of the stereociliary mechanoelectrical transduction (MET) channel. Although both PLS1-knockout zebrafish and zebrafish expressing ΔExon8-PLS1 exhibited behavioral signs of hearing impairment, defects in MET channel uptake were observed only in the mutant-expressing fish. Notably, neither PLS1 deficiency nor re-expression of human wild-type PLS1 in knockout zebrafish reproduces this MET defect. Thus, the mutation not only reduces native PLS1 function but also interferes with normal MET channel activity.
HostingRepository	PRIDE
AnnounceDate	2026-05-21
AnnouncementXML	Submission_2026-05-21_00:14:21.176.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tingting Xu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	6220 Time-of-Flight LC/MS; MALDI Synapt MS; Synapt MS; Q Exactive HF; LCQ Classic; TripleTOF 5600; 6410 Triple Quadrupole LC/MS; Q Exactive; LTQ Orbitrap; 4800 Proteomics Analyzer; 6340 Ion Trap LC/MS; Orbitrap Fusion Lumos; LTQ; LTQ Orbitrap Velos; Q TRAP; Q-Tof Ultima; maXis; timsTOF Pro; LTQ FT; autoflex; ultraflex; QSTAR; 4700 Proteomics Analyzer; Orbitrap Fusion; 6520A Quadrupole Time-of-Flight LC/MS; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-25 13:01:44	ID requested
⏵ 1	2026-05-21 00:14:21	announced

10.1038/S41598-026-47079-4;

submitter keyword: PLS1

ACTG1

MYO1C

xu tingting
contact affiliation	1The First Department of Clinical Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian Province, China. 2Medical Genetic Diagnosis and Therapy Center of Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian Provincial Key Laboratory of Prenatal Diagnosis and Birth Defects, Fuzhou 350001, Fujian Province, China.
contact email	15959156211@163.com
lab head
Tingting Xu
contact affiliation	The First Department of Clinical Medicine, Fujian University of Traditional Chinese Medicine
contact email	15959156211@163.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/05/PXD076160

PRIDE project URI

• PRIDE
  1. PXD076160
     1. Label: PRIDE project
     2. Name: Pathogenic Mechanism of the PLS1 Gene Variant in Hearing Loss and Functional Validation in a Zebrafish Model