The dynamics of MAPK inactivation at fertilization in mouse eggs

Gonzalez-Garcia, Jose Raul, Bradley, Josephine, Nomikos, Michail, Paul, Laboni, Machaty, Zoltan, Lai, F. Anthony ORCID: https://orcid.org/0000-0003-2852-8547 and Swann, Karl ORCID: https://orcid.org/0000-0002-4355-1449 2014. The dynamics of MAPK inactivation at fertilization in mouse eggs. Journal of Cell Science 127 (12) , pp. 2749-2760. 10.1242/jcs.145045

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Abstract

Egg activation at fertilization in mammals is initiated by prolonged Ca2+ oscillations that trigger the completion of meiosis and formation of pronuclei. A fall in mitogen-activated protein kinase (MAPK) activity is essential for pronuclear formation, but the precise timing and mechanism of decline are unknown. Here, we have measured the dynamics of MAPK pathway inactivation during fertilization of mouse eggs using novel chemiluminescent MAPK activity reporters. This reveals that the MAPK activity decrease begins during the Ca2+ oscillations, but MAPK does not completely inactivate until after pronuclear formation. The MAPKs present in eggs are Mos, MAP2K1 and MAP2K2 (MEK1 and MEK2, respectively) and MAPK3 and MAPK1 (ERK1 and ERK2, respectively). Notably, the MAPK activity decline at fertilization is not explained by upstream destruction of Mos, because a decrease in the signal from a Mos–luciferase reporter is not associated with egg activation. Furthermore, Mos overexpression does not affect the timing of MAPK inactivation or pronuclear formation. However, the late decrease in MAPK could be rapidly reversed by the protein phosphatase inhibitor, okadaic acid. These data suggest that the completion of meiosis in mouse zygotes is driven by an increased phosphatase activity and not by a decline in Mos levels or MEK activity.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Medicine
Subjects:	R Medicine > R Medicine (General)
Additional Information:	This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Publisher:	Company of Biologists
ISSN:	0021-9533
Funders:	Wellcome Trust
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	25 March 2014
Last Modified:	12 Jun 2024 06:51
URI:	https://orca.cardiff.ac.uk/id/eprint/61197

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