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Updated: Jul 29, 2026

Meiotic Spindle Assessment in Mouse Oocytes by siRNA-mediated Silencing
Published on: October 11, 2015
Mos activates MAP kinase in mouse oocytes through two opposite pathways
M H Verlhac1, C Lefebvre, J Z Kubiak
1Biologie Cellulaire et Moléculaire du Développement, UMR 7622, CNRS/Université Pierre et Marie Curie, 9 quai Saint Bernard-Bat. C-5, 75252 Paris, cedex 05, France.
Abstract:
Activation of mitogen-activated protein kinase (MAPK) in maturing mouse oocytes occurs after synthesis of Mos, a MAPKKK. To investigate whether Mos acts only through MEK1, we microinjected constitutively active forms of MEK1 (MEK1S218D/S222D referred herein as MEK*) and Raf (DeltaRaf) into mouse oocytes. In mos(-/-) oocytes, which do not activate MAPK during meiosis and do not arrest in metaphase II, MEK* and DeltaRaf did not rescue MAPK activation and metaphase II arrest, whereas Mos induced a complete rescue. MEK* and DeltaRaf induced cleavage arrest of two-cell blastomeres. They induced MAPK activation when protein phosphatases were inhibited by okadaic acid, suggesting that Mos may inhibit protein phosphatases. Finally, in mos(-/-) oocytes, MEK* induced the phosphorylation of Xp42(mapk)D324N, a mutant less sensitive to dephosphorylation, showing that a MAPK phosphatase activity is present in mouse oocytes. We demonstrate that active MAPKK or MAPKKK cannot substitute for Mos to activate MAPK in mouse oocytes. We also show that a phosphatase activity inactivates MAPK, and that Mos can overcome this inhibitory activity. Thus Mos activates MAPK through two opposite pathways: activation of MEK1 and inhibition of a phosphatase.
Insights
Mos is crucial for mouse oocyte maturation, activating mitogen-activated protein kinase (MAPK) through both MEK1 activation and phosphatase inhibition. This study reveals Mos
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- Mitogen-activated protein kinase (MAPK) activation is essential for mouse oocyte maturation.
- Mos, a MAPKKK, plays a key role in this process.
- The precise mechanism by which Mos activates MAPK remains incompletely understood.
Purpose of the Study:
- To investigate whether Mos activates MAPK solely through MEK1.
- To elucidate the role of Mos in regulating MAPK activity and oocyte maturation.
- To identify potential downstream effectors and regulatory pathways of Mos.
Main Methods:
- Microinjection of constitutively active MEK1 (MEK*) and Raf (DeltaRaf) into mouse oocytes.
- Analysis of MAPK activation and metaphase II arrest in wild-type and mos(-/-) oocytes.
- Assessment of oocyte maturation and cleavage arrest following microinjection.
- Inhibition of protein phosphatases using okadaic acid.
Main Results:
- MEK* and DeltaRaf failed to rescue MAPK activation and metaphase II arrest in mos(-/-) oocytes.
- Mos successfully rescued MAPK activation and metaphase II arrest in mos(-/-) oocytes.
- MEK* and DeltaRaf induced MAPK activation when protein phosphatases were inhibited.
- A MAPK phosphatase activity was identified in mouse oocytes, which Mos can overcome.
Conclusions:
- Active MAPKK or MAPKKK cannot substitute for Mos in activating MAPK in mouse oocytes.
- Mos activates MAPK through a dual pathway: activating MEK1 and inhibiting a phosphatase.
- Mos plays a critical role in regulating MAPK activity and ensuring proper oocyte maturation.
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