ZMYND12 serves as an IDAd subunit that is essential for sperm motility in mice.
Cell Mol Life Sci
; 81(1): 317, 2024 Jul 27.
Article
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| MEDLINE
| ID: mdl-39066891
ABSTRACT
Inner dynein arms (IDAs) are formed from a protein complex that is essential for appropriate flagellar bending and beating. IDA defects have previously been linked to the incidence of asthenozoospermia (AZS) and male infertility. The testes-enriched ZMYND12 protein is homologous with an IDA component identified in Chlamydomonas. ZMYND12 deficiency has previously been tied to infertility in males, yet the underlying mechanism remains uncertain. Here, a CRISPR/Cas9 approach was employed to generate Zmynd12 knockout (Zmynd12-/-) mice. These Zmynd12-/- mice exhibited significant male subfertility, reduced sperm motile velocity, and impaired capacitation. Through a combination of co-immunoprecipitation and mass spectrometry, ZMYND12 was found to interact with TTC29 and PRKACA. Decreases in the levels of PRKACA were evident in the sperm of these Zmynd12-/- mice, suggesting that this change may account for the observed drop in male fertility. Moreover, in a cohort of patients with AZS, one patient carrying a ZMYND12 variant was identified, expanding the known AZS-related variant spectrum. Together, these findings demonstrate that ZMYND12 is essential for flagellar beating, capacitation, and male fertility.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Motilidad Espermática
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Ratones Noqueados
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Infertilidad Masculina
Límite:
Animals
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Humans
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Male
Idioma:
En
Año:
2024
Tipo del documento:
Article