C2CD6 regulates targeting and organization of the CatSper calcium channel complex in sperm flagella.
Development
; 149(2)2022 01 15.
Article
in En
| MEDLINE
| ID: mdl-34919125
ABSTRACT
The CatSper cation channel is essential for sperm capacitation and male fertility. The multi-subunit CatSper complexes form highly organized calcium signaling nanodomains on flagellar membranes. Here, we report identification of an uncharacterized protein, C2CD6, as a subunit of the mouse CatSper complex. C2CD6 contains a calcium-dependent, membrane-targeting C2 domain. C2CD6 associates with the CatSper calcium-selective, core-forming subunits. Deficiency of C2CD6 depletes the CatSper nanodomains from the flagellum and results in male sterility. C2CD6-deficient sperm are defective in hyperactivation and fail to fertilize oocytes both in vitro and in vivo. CatSper currents are present but at a significantly lower level in C2CD6-deficient sperm. Transient treatments with either Ca2+ ionophore, starvation, or a combination of both restore the fertilization capacity of C2CD6-deficient sperm. C2CD6 interacts with EFCAB9, a pH-dependent calcium sensor in the CatSper complex. We postulate that C2CD6 facilitates incorporation of the CatSper complex into the flagellar plasma membrane and may function as a calcium sensor. The identification of C2CD6 may enable the long-sought reconstitution of the CatSper ion channel complex in a heterologous system for male contraceptive development.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sperm Tail
/
Calcium Channels
/
Infertility, Male
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Development
Journal subject:
BIOLOGIA
/
EMBRIOLOGIA
Year:
2022
Type:
Article
Affiliation country:
United States