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

Content Provider	Europe PMC
Author	Reynoso, Sequoyah Castillo, Vanessa Katkar, Gajanan Dattatray Lopez-Sanchez, Inmaculada Taheri, Sahar Espinoza, Celia Rohena, Cristina Sahoo, Debashis Gagneux, Pascal Ghosh, Pradipta
Editor	Cooper, Jonathan A
Copyright Year	2021
Abstract	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.
Journal	eLife
Volume Number	10
PubMed Central reference number	PMC8376251
PubMed reference number	34409938
e-ISSN	2050084X
DOI	10.7554/elife.69160
Language	English
Publisher	eLife Sciences Publications, Ltd
Publisher Date	2021-08-19
Access Restriction	Open
Rights License	This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. © 2021, Reynoso et al
Subject Keyword	Girdin Sperm male fertility spermatozoa cAMP Human Mouse
Content Type	Text
Resource Type	Article
Subject	Immunology and Microbiology Neuroscience Medicine Biochemistry, Genetics and Molecular Biology

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