ArticlebioRxiv : the preprint server for biology2025
SPINK3-sperm interaction determines a stable sperm subpopulation with intact CatSper channel: SPINK3 stabilizes CatSper1 and membrane.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Sperm capacitation involves proteolytic remodeling of membrane proteins, including components of the CatSper calcium channel, which is essential for hyperactivation and male fertility. Here, we identify the seminal protease inhibitor SPINK3, a known decapacitation factor that suppresses premature capacitation in the female tract, as the first physiological inhibitor of CATSPER1 processing. In mouse sperm, SPINK3 blocks capacitation-induced CATSPER1 cleavage, preserving a subpopulation with intact CatSper channels and lacking pTyr development in the flagellum. SPINK3 localizes to the outer surface of the sperm principal piece membrane in a CatSper-dependent but non-quadrilateral pattern, stabilizes membrane organization, and delays cholesterol efflux. These results reveal SPINK3 as a multifunctional regulator of capacitation, shaping sperm subpopulations in the female reproductive tract.
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