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Functional disparity between human PAWP and PLCζ in the generation of Ca2+ oscillations for oocyte activation

Nomikos, Michail, Sanders, Jessica R., Kashir, Junaid, Sanusi, Randa, Buntwal, Luke, Love, Daniel, Ashley, Peter, Sanders, David, Knaggs, Paul, Bunkheila, Adnan, Swann, Karl and Lai, Francis 2015. Functional disparity between human PAWP and PLCζ in the generation of Ca2+ oscillations for oocyte activation. Molecular Human Reproduction 21 (9) , pp. 702-710. 10.1093/molehr/gav034

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Mammalian oocyte activation is mediated by cytosolic calcium (Ca2+) oscillations initiated upon delivery of a putative ‘sperm factor’ by the fertilizing sperm. Previous studies suggest the identity of this sperm factor as the testis-specific phospholipase C-zeta (PLCζ). Recently, a post-acrosomal sheath WW domain-binding protein (PAWP) has been proposed as an alternative sperm factor candidate, following a report that human PAWP protein and cRNA elicited Ca2+ oscillations in mouse and human oocytes. Those Ca2+ oscillations were inhibited by a PAWP-derived peptide corresponding to a functional PPGY binding motif. Herein, using a series of human PAWP expression constructs, we demonstrate that both human PAWP protein and cRNA are, in our experiments, unable to elicit Ca2+ release following microinjection into mouse oocytes. Parallel experiments performed with human PLCζ elicited the characteristic Ca2+ oscillations present at mammalian fertilization, which produced oocyte activation and embryo development. Furthermore, sperm-induced Ca2+ oscillations were not inhibited by the PAWP-derived PPGY peptide following in vitro fertilization or intracytoplasmic sperm injection. Thus, the functional disparity with PLCζ leads us to conclude that human PAWP is neither sufficient nor necessary for the Ca2+ oscillations that initiate mammalian oocyte activation at fertilization.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: R Medicine > R Medicine (General)
Publisher: Oxford University Press
ISSN: 1360-9947
Date of Acceptance: 19 June 2015
Last Modified: 17 May 2022 09:54

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