Homeodomain-interacting protein kinase HIPK4 regulates phosphorylation of manchette protein RIMBP3 during spermiogenesis.
J Biol Chem
; 298(9): 102327, 2022 09.
Article
em En
| MEDLINE
| ID: mdl-35931115
ABSTRACT
Nonobstructive azoospermia (NOA) is the most serious form of spermatogenesis abnormalities in male infertility. Genetic factors are important to consider as elements leading to NOA. Although many pathogenic genes have been reported, the causative genes of NOA for many patients are still unknown. In this study, we found ten point mutations in the gene encoding homeodomain-interacting protein kinase 4 (HIPK4) in patients with NOA, and using in vitro studies, we determined a premature termination point mutation (p. Lys490∗, c.1468A>T) that can cause decreased expression of HIPK4. Our phosphoproteomic analysis of Hipk4-/- testes revealed phosphorylation of multiple proteins regulated by HIPK4 during spermiogenesis. We also confirmed that a substrate of HIPK4 with four downregulated phosphorylation sites matching the xSPx motif is the known manchette-related protein RIMS-binding protein 3, which is required for sperm head morphogenesis. Therefore, we conclude HIPK4 regulates the phosphorylation of manchette protein RIMS-binding protein 3 and plays essential roles in sperm head shaping and male fertility.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cabeça do Espermatozoide
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Espermatogênese
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Proteínas Serina-Treonina Quinases
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Códon sem Sentido
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Proteínas do Citoesqueleto
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Azoospermia
Limite:
Humans
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Male
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China