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

Abstract:

BACKGROUND INFORMATION:At fertilization in mammalian eggs, the sperm induces a series of Ca(2+) 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 PLCzeta (phospholipase C-zeta) that enters the egg after gamete fusion. The specific phosphatidylinositol 4,5-bisphosphate hydrolytic activity of PLCzeta 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 PLCzeta- 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 PLCzeta, was barely detectable. However, when PLCzeta is overexpressed in eggs, significant plasma-membrane DAG production occurs in concert with a series of unexpected secondary high-frequency Ca(2+) oscillations. We show that these secondary Ca(2+) 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 Ca(2+) oscillations appears to involve Ca(2+) influx and the loading of thapsigargin-sensitive Ca(2+) stores. CONCLUSIONS:Our results suggest that overproduction of DAG in PLCzeta-injected eggs can lead to PKC-mediated Ca(2+) influx and subsequent overloading of Ca(2+) stores. These results suggest that DAG generation in the plasma membrane of fertilizing mouse eggs is minimized since it can perturb egg Ca(2+) homoeostasis via excessive Ca(2+) influx.

journal_name

Biol Cell

journal_title

Biology of the cell

authors

Yu Y,Halet G,Lai FA,Swann K

doi

10.1042/BC20080033

subject

Has Abstract

pub_date

2008-11-01 00:00:00

pages

633-43

issue

11

eissn

0248-4900

issn

1768-322X

pii

BC20080033

journal_volume

100

pub_type

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