PXD025330

PXD025330 is an original dataset announced via ProteomeXchange.

Title	CEP128 mutations impair spermatogenesis in humans and mice
Description	The centrosome is a conserved eukaryotic organelle essential to the reproductive process, and centrosomal proteins are necessary for the components of the centrosome. However, few centrosomal proteins have been genetically linked to fertility, and the related molecular mechanisms remain unknown. Here, we identified a novel homozygous missense mutation of CEP128 (c.665G>A [p.R222Q]) in two infertile males with cryptozoospermia from a consanguineous family. This variant abnormally increased CEP128 protein expression. Remarkably, mouse models harbouring the orthologous variant of CEP128 R222Q were sterile, showing anomalies in the sperm morphology, count and motility. To confirm the important role of CEP128 in male fertility, we also generated Cep128 knock-out (KO) male mice, which were infertile associated with the disrupted sperm quality. Importantly, the defective sperm flagella were obviously observed in the two mouse strains, while the number, morphology and ultrastructure of cilia in other organs were normal, suggesting that CEP128 mutations only affect ciliogenesis in testes. Mechanistically, the imbalance expression of CEP128, whatever increase or decrease, perturbed the normal expression of genes and/or the phosphorylation of TGF-β/BMP signaling members involved in spermatogenesis. Altogether, our findings unprecedentedly unveil a crucial role for CEP128 in male fertility and provide new insights into the functions of centrosomal proteins in human disease.
HostingRepository	PRIDE
AnnounceDate	2022-05-20
AnnouncementXML	Submission_2022-05-19_22:32:11.900.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	zhang zhiwei
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-12 19:33:23	ID requested
⏵ 1	2022-05-19 22:32:12	announced

Zhang X, Wang L, Ma Y, Wang Y, Liu H, Liu M, Qin L, Li J, Jiang C, Zhang X, Shan X, Liu Y, Li J, Li Y, Zheng R, Sun Y, Sun J, Leng X, Liang Y, Zhang F, Jiang X, Yang Y, Shen Y, CEP128 is involved in spermatogenesis in humans and mice. Nat Commun, 13(1):1395(2022) [pubmed]

submitter keyword: CEP128

infertility

spermatogenesis

centrosome

Shen Ying
contact affiliation	West China Second University Hospital, Sichuan University
contact email	yingcaishen01@163.com
lab head
zhang zhiwei
contact affiliation	sichuan university
contact email	university_mr01@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/2022/05/PXD025330

PRIDE project URI

• PRIDE
  1. PXD025330
     1. Label: PRIDE project
     2. Name: CEP128 mutations impair spermatogenesis in humans and mice