Proteomics

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Dysfunction of CEP128 impairs spermatogenesis but not ciliogenesis in humans and mice

ABSTRACT: The centrosome is a conserved eukaryotic organelle essential for reproductive process, and centrosomal proteins (CEP) are necessary for composition of the centrosome. However, few CEPs have been genetically linked to fertility, and the related molecular mechanisms remains mysterious. Here, we identified a new CEP, CEP128, which is functional in spermatogenesis, fertilization and embryonic development in both humans and mice. The variants of CEP128/Cep128 could lead to aberrant centrosome structures of the sperm inducing to anomalies in sperm morphology, count as well as motility, and further result in male infertility, but did not grossly affect ciliogenesis. Mechanistically, both loss and up-regulation of CEP128 could cause suppressed expressions of the genes involved in the spermatogenesis and fertilization phase. Altogether, our findings unprecedentedly unveil a crucial role of CEP128 in male fertility and provides new insight into the function of CEPs in human disease.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Testis

SUBMITTER: Jichang Huang  

LAB HEAD: Ying Shen

PROVIDER: PXD022731 | Pride | 2022-05-19

REPOSITORIES: Pride

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Centrosomal proteins are necessary components of the centrosome, a conserved eukaryotic organelle essential to the reproductive process. However, few centrosomal proteins have been genetically linked to fertility. Herein we identify a homozygous missense variant of CEP128 (c.665 G > A [p.R222Q]) in two infertile males. Remarkably, male homozygous knock-in mice harboring the orthologous CEP128<sup>R222Q</sup> variant show anomalies in sperm morphology, count, and motility. Moreover, Cep128 knock-  ...[more]

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