GIV/Girdin, a non-receptor modulator for G[alpha]i/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...

Full description

Saved in:
Bibliographic Details
Published in:eLife 2021-08, Vol.10
Main Authors: Reynoso, Sequoyah, Castillo, Vanessa, Katkar, Gajanan Dattatray, Lopez-Sanchez, Inmaculada, Taheri, Sahar, Espinoza, Celia, Rohena, Cristina, Sahoo, Debashis, Gagneux, Pascal, Ghosh, Pradipta
Format: Article
Language:English
Subjects:
Cyclic adenylic acid
G proteins
Spermatozoa
Tyrosine
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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[right arrow]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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.69160