Regulation of diacylglycerol production and protein kinase C stimulation during sperm- and PLCζ-mediated mouse egg activation

Yu, Yuansong, Halet, Guillaume, Lai, Francis Anthony ORCID: https://orcid.org/0000-0003-2852-8547 and Swann, Karl ORCID: https://orcid.org/0000-0002-4355-1449 2008. Regulation of diacylglycerol production and protein kinase C stimulation during sperm- and PLCζ-mediated mouse egg activation. Biology of the Cell 100 (11) , pp. 633-643. 10.1042/BC20080033

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Abstract

Background information. At fertilization in mammalian eggs, the sperm induces a series of Ca2+ oscillations via the production of inositol 1,4,5-trisphosphate. Increased inositol 1,4,5-trisphosphate production appears to be triggered by a sperm-derived PLCζ (phospholipase C-ζ) that enters the egg after gamete fusion. The specific phosphatidylinositol 4,5-bisphosphate hydrolytic activity of PLCζ implies that DAG (diacylglycerol) production, and hence PKC (protein kinase C) stimulation, also occurs during mammalian egg fertilization. Fertilization-mediated increase in PKC activity has been demonstrated; however, its precise role is unclear. Results. We investigated PLCζ- and fertilization-mediated generation of DAG in mouse eggs by monitoring plasma-membrane translocation of a fluorescent DAG-specific reporter. Consistent plasma-membrane DAG formation at fertilization, or after injection of physiological concentrations of PLCζ, was barely detectable. However, when PLCζ is overexpressed in eggs, significant plasma-membrane DAG production occurs in concert with a series of unexpected secondary high-frequency Ca2+ oscillations. We show that these secondary Ca2+ oscillations can be mimicked in a variety of situations by the stimulation of PKC and that they can be prevented by PKC inhibition. The way PKC leads to secondary Ca2+ oscillations appears to involve Ca2+ influx and the loading of thapsigargin-sensitive Ca2+ stores. Conclusions. Our results suggest that overproduction of DAG in PLCζ-injected eggs can lead to PKC-mediated Ca2+ influx and subsequent overloading of Ca2+ stores. These results suggest that DAG generation in the plasma membrane of fertilizing mouse eggs is minimized since it can perturb egg Ca2+ homoeostasis via excessive Ca2+ influx.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	Q Science > QH Natural history > QH426 Genetics Q Science > QR Microbiology R Medicine > RG Gynecology and obstetrics
Uncontrolled Keywords:	Ca2+ store; diacylglycerol; egg activation; fertilization; protein kinase C; phospholipase C-ζ (PLCζ)
Publisher:	Wiley Blackwell
ISSN:	0248-4900
Last Modified:	19 Oct 2022 10:39
URI:	https://orca.cardiff.ac.uk/id/eprint/25128

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