title: CRISP1 as a novel CatSper regulator that modulates sperm motility and orientation during fertilization.
abstract: 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.
authors.affiliation: Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, C1428ADN Buenos Aires, Argentina.
authors.forename: Juan I
authors.initials: JI
authors.lastname: Ernesto
authors.affiliation: Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, C1428ADN Buenos Aires, Argentina.
authors.forename: Mariana
authors.initials: M
authors.lastname: Weigel Muñoz
authors.affiliation: Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, C1428ADN Buenos Aires, Argentina.
authors.forename: María A
authors.initials: MA
authors.lastname: Battistone
authors.affiliation: Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, C1428ADN Buenos Aires, Argentina.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Vasen
authors.affiliation: Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Morelos 62250, México.
authors.forename: Pablo
authors.initials: P
authors.lastname: Martínez-López
authors.affiliation: Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Morelos 62250, México.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Orta
authors.affiliation: Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Morelos 62250, México.
authors.forename: Dulce
authors.initials: D
authors.lastname: Figueiras-Fierro
authors.affiliation: Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Morelos 62250, México.
authors.forename: José L
authors.initials: JL
authors.lastname: De la Vega-Beltran
authors.affiliation: Fertility Patagonia, 8400 San Carlos de Bariloche, Argentina.
authors.forename: Ignacio A
authors.initials: IA
authors.lastname: Moreno
authors.affiliation: Centro de Biología Celular y Molecular, Instituto de Investigaciones Biológicas y Tecnológicas, Universidad Nacional de Córdoba, X5016GCA Córdoba, Argentina.
authors.forename: Héctor A
authors.initials: HA
authors.lastname: Guidobaldi
authors.affiliation: Centro de Biología Celular y Molecular, Instituto de Investigaciones Biológicas y Tecnológicas, Universidad Nacional de Córdoba, X5016GCA Córdoba, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Giojalas
authors.affiliation: Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Morelos 62250, México.
authors.forename: Alberto
authors.initials: A
authors.lastname: Darszon
authors.affiliation: Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, C1428ADN Buenos Aires, Argentina.
authors.forename: Débora J
authors.initials: DJ
authors.lastname: Cohen
authors.affiliation: Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, C1428ADN Buenos Aires, Argentina pcuasnicu@ibyme.conicet.gov.ar pcuasnicu@gmail.com.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Cuasnicú
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D005260:Female; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D013081:Sperm Motility / Q000502:physiology*; D013084:Sperm-Ovum Interactions / Q000502:physiology*; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; C488642:Catsper1 protein, mouse; C486321:Crisp1 protein, mouse; D008562:Membrane Glycoproteins; D002118:Calcium