Identification of IQCH as a calmodulin-associated protein required for sperm motility in humans.
iScience
; 26(8): 107354, 2023 Aug 18.
Article
em En
| MEDLINE
| ID: mdl-37520705
ABSTRACT
Sperm fertilization ability mainly relies on proper sperm progression through the female genital tract and capacitation, which involves phosphorylation signaling pathways triggered by calcium and bicarbonate. We performed exome sequencing of an infertile asthenozoospermic patient and identified truncating variants in MAP7D3, encoding a microtubule-associated protein, and IQCH, encoding a protein of unknown function with enzymatic and signaling features. We demonstrate the deleterious impact of both variants on sperm transcripts and proteins from the patient. We show that, in vitro, patient spermatozoa could not induce the phosphorylation cascades associated with capacitation. We also provide evidence for IQCH association with calmodulin, a well-established calcium-binding protein that regulates the calmodulin kinase. Notably, we describe IQCH spatial distribution around the sperm axoneme, supporting its function within flagella. Overall, our work highlights the cumulative pathological impact of gene mutations and identifies IQCH as a key protein required for sperm motility and capacitation.
Texto completo:
1
Base de dados:
MEDLINE
Tipo de estudo:
Diagnostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
IScience
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
França