CRISP1 AS A NOVEL CATSPER REGULATOR THAT MODULATES SPERM MOTILITY AND ORIENTATION DURING FERTILIZATION

JUAN I. ERNESTO ; MARIANA WEIGEL MUÑOZ; MARÍA A. BATTISTONE; GUSTAVO VASEN; PABLO MARTÍNEZ-LÓPEZ ; GERARDO ORTA; DULCE FIGUEIRAS-FIERRO; JOSÉ L. DE LA VEGA-BELTRAN; IGNACIO A. MORENO3,; HÉCTOR A. GUIDOBALDI; LUDMILA CURCI; GUILLERMO CARAVAJAL; LAURA GIOJALAS; ALBERTO DARSZON; DÉBORA J. COHEN; PATRICIA S. CUASNICÚ

Conferencia; Gordon Research Conference; 2015

Ca(2+)-dependent mechanisms are critical for successful completion of fertilization. Here, we demonstrate that CRISP1, a sperm protein involved in mammalian fertilization, is also present in the female gamete and capable of modulating key sperm Ca(2+) channels. Specifically, we show that CRISP1 is expressed by the cumulus cells that surround the egg and that fertilization of cumulus-oocyte complexes from CRISP1 knockout females is impaired because of a failure of sperm to penetrate the cumulus. We provide evidence that CRISP1 stimulates sperm orientation by modulating sperm hyperactivation, a vigorous motility required for penetration of the egg vestments. Moreover, patch clamping of sperm revealed that CRISP1 has the ability to regulate CatSper, the principal sperm Ca(2+) channel involved in hyperactivation and essential for fertility. Given the critical role of Ca(2+) for sperm motility, we propose a novel CRISP1-mediated fine-tuning mechanism to regulate sperm hyperactivation and orientation for successful penetration of the cumulus during fertilization.