GIV/Girdin, a non-receptor modulator for Gαi/s, regulates spatiotemporal signaling during sperm capacitation and is required for male fertility

For a sperm to successfully fertilize an egg, it must first undergo capacitation in the female reproductive tract and later undergo acrosomal reaction (AR) upon encountering an egg surrounded by its vestment. How premature AR is avoided despite rapid surges in signaling cascades during capacitation...

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Autores principales:	Sequoyah Reynoso, Vanessa Castillo, Gajanan Dattatray Katkar, Inmaculada Lopez-Sanchez, Sahar Taheri, Celia Espinoza, Cristina Rohena, Debashis Sahoo, Pascal Gagneux, Pradipta Ghosh
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	Girdin Sperm male fertility spermatozoa cAMP Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5ebcf3910b234be9bef6d60f2c3ce120
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spelling	oai:doaj.org-article:5ebcf3910b234be9bef6d60f2c3ce1202021-11-26T11:13:13ZGIV/Girdin, a non-receptor modulator for Gαi/s, regulates spatiotemporal signaling during sperm capacitation and is required for male fertility10.7554/eLife.691602050-084Xe69160https://doaj.org/article/5ebcf3910b234be9bef6d60f2c3ce1202021-08-01T00:00:00Zhttps://elifesciences.org/articles/69160https://doaj.org/toc/2050-084XFor a sperm to successfully fertilize an egg, it must first undergo capacitation in the female reproductive tract and later undergo acrosomal reaction (AR) upon encountering an egg surrounded by its vestment. How premature AR is avoided despite rapid surges in signaling cascades during capacitation remains unknown. Using a combination of conditional knockout (cKO) mice and cell-penetrating peptides, we show that GIV (CCDC88A), a guanine nucleotide-exchange modulator (GEM) for trimeric GTPases, is highly expressed in spermatocytes and is required for male fertility. GIV is rapidly phosphoregulated on key tyrosine and serine residues in human and murine spermatozoa. These phosphomodifications enable GIV-GEM to orchestrate two distinct compartmentalized signaling programs in the sperm tail and head; in the tail, GIV enhances PI3K→Akt signals, sperm motility and survival, whereas in the head it inhibits cAMP surge and premature AR. Furthermore, GIV transcripts are downregulated in the testis and semen of infertile men. These findings exemplify the spatiotemporally segregated signaling programs that support sperm capacitation and shed light on a hitherto unforeseen cause of infertility in men.Sequoyah ReynosoVanessa CastilloGajanan Dattatray KatkarInmaculada Lopez-SanchezSahar TaheriCelia EspinozaCristina RohenaDebashis SahooPascal GagneuxPradipta GhosheLife Sciences Publications LtdarticleGirdinSpermmale fertilityspermatozoacAMPMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Girdin Sperm male fertility spermatozoa cAMP Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	Girdin Sperm male fertility spermatozoa cAMP Medicine R Science Q Biology (General) QH301-705.5 Sequoyah Reynoso Vanessa Castillo Gajanan Dattatray Katkar Inmaculada Lopez-Sanchez Sahar Taheri Celia Espinoza Cristina Rohena Debashis Sahoo Pascal Gagneux Pradipta Ghosh GIV/Girdin, a non-receptor modulator for Gαi/s, regulates spatiotemporal signaling during sperm capacitation and is required for male fertility
description	For a sperm to successfully fertilize an egg, it must first undergo capacitation in the female reproductive tract and later undergo acrosomal reaction (AR) upon encountering an egg surrounded by its vestment. How premature AR is avoided despite rapid surges in signaling cascades during capacitation remains unknown. Using a combination of conditional knockout (cKO) mice and cell-penetrating peptides, we show that GIV (CCDC88A), a guanine nucleotide-exchange modulator (GEM) for trimeric GTPases, is highly expressed in spermatocytes and is required for male fertility. GIV is rapidly phosphoregulated on key tyrosine and serine residues in human and murine spermatozoa. These phosphomodifications enable GIV-GEM to orchestrate two distinct compartmentalized signaling programs in the sperm tail and head; in the tail, GIV enhances PI3K→Akt signals, sperm motility and survival, whereas in the head it inhibits cAMP surge and premature AR. Furthermore, GIV transcripts are downregulated in the testis and semen of infertile men. These findings exemplify the spatiotemporally segregated signaling programs that support sperm capacitation and shed light on a hitherto unforeseen cause of infertility in men.
format	article
author	Sequoyah Reynoso Vanessa Castillo Gajanan Dattatray Katkar Inmaculada Lopez-Sanchez Sahar Taheri Celia Espinoza Cristina Rohena Debashis Sahoo Pascal Gagneux Pradipta Ghosh
author_facet	Sequoyah Reynoso Vanessa Castillo Gajanan Dattatray Katkar Inmaculada Lopez-Sanchez Sahar Taheri Celia Espinoza Cristina Rohena Debashis Sahoo Pascal Gagneux Pradipta Ghosh
author_sort	Sequoyah Reynoso
title	GIV/Girdin, a non-receptor modulator for Gαi/s, regulates spatiotemporal signaling during sperm capacitation and is required for male fertility
title_short	GIV/Girdin, a non-receptor modulator for Gαi/s, regulates spatiotemporal signaling during sperm capacitation and is required for male fertility
title_full	GIV/Girdin, a non-receptor modulator for Gαi/s, regulates spatiotemporal signaling during sperm capacitation and is required for male fertility
title_fullStr	GIV/Girdin, a non-receptor modulator for Gαi/s, regulates spatiotemporal signaling during sperm capacitation and is required for male fertility
title_full_unstemmed	GIV/Girdin, a non-receptor modulator for Gαi/s, regulates spatiotemporal signaling during sperm capacitation and is required for male fertility
title_sort	giv/girdin, a non-receptor modulator for gαi/s, regulates spatiotemporal signaling during sperm capacitation and is required for male fertility
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/5ebcf3910b234be9bef6d60f2c3ce120
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GIV/Girdin, a non-receptor modulator for Gαi/s, regulates spatiotemporal signaling during sperm capacitation and is required for male fertility

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