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Mos in the oocyte: how to use MAPK independently of growth factors and transcription to control meiotic divisions.

Dupré A, Haccard O, Jessus C - J Signal Transduct (2010)

Bottom Line: In one specific cell type however, the female germ cell, MAPK does not follow this canonical scheme.Which unique functions could explain the evolutionary cost to have selected one gene to only serve for few hours in one very specific cell type?This review discusses the original features of MAPK activation by Mos and the roles of this module in oocytes.

View Article: PubMed Central - PubMed

Affiliation: CNRS, UMR 7622-Biologie du Développement, 9 Quai Saint-Bernard, 75005 Paris, France.

ABSTRACT
In many cell types, the mitogen-activated protein kinase (MAPK) also named extracellular signal-regulated kinase (ERK) is activated in response to a variety of extracellular growth factor-receptor interactions and leads to the transcriptional activation of immediate early genes, hereby influencing a number of tissue-specific biological activities, as cell proliferation, survival and differentiation. In one specific cell type however, the female germ cell, MAPK does not follow this canonical scheme. In oocytes, MAPK is activated independently of growth factors and tyrosine kinase receptors, acts independently of transcriptional regulation, plays a crucial role in controlling meiotic divisions, and is under the control of a peculiar upstream regulator, the kinase Mos. Mos was originally identified as the transforming gene of Moloney murine sarcoma virus and its cellular homologue was the first proto-oncogene to be molecularly cloned. What could be the specific roles of Mos that render it necessary for meiosis? Which unique functions could explain the evolutionary cost to have selected one gene to only serve for few hours in one very specific cell type? This review discusses the original features of MAPK activation by Mos and the roles of this module in oocytes.

No MeSH data available.


Related in: MedlinePlus

Meiotic arrest of the unfertilized oocyte: the downstream effectors of Mos/MAPK. In all species, oocytes halt meiosis to prevent embryonic development in the absence of fertilization. Depending on species, meiosis arrests at prophase I, metaphase I, metaphase II, or G1 following meiosis. Except in C. elegans, Mos was found to be the ubiquitous cytostatic factor responsible for the unfertilized oocyte arrest. Its downstream targets accounting for the meiotic arrest of the unfertilized oocytes are indicated.
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fig3: Meiotic arrest of the unfertilized oocyte: the downstream effectors of Mos/MAPK. In all species, oocytes halt meiosis to prevent embryonic development in the absence of fertilization. Depending on species, meiosis arrests at prophase I, metaphase I, metaphase II, or G1 following meiosis. Except in C. elegans, Mos was found to be the ubiquitous cytostatic factor responsible for the unfertilized oocyte arrest. Its downstream targets accounting for the meiotic arrest of the unfertilized oocytes are indicated.

Mentions: In vertebrates, the Mos/MAPK pathway serves to stabilize MPF, ensuring an arrest at the metaphase stage. Releasing this blockage requires the activity of the APC/C protein complex, a ubiquitin ligase that targets cyclin B for destruction [108, 109]. In mouse and Xenopus metaphase II-arrested oocytes, APC/C is directly inhibited by the Erp1/Emi2 protein [110]. During oocyte maturation, Erp1/Emi2 appears only after metaphase I, explaining why the oocyte does not stop at metaphase I, but at metaphase II [111, 112]. Upon fertilization, a transient rise in free intracellular calcium activates calmodulin-dependent protein kinase II that phosphorylates Erp1/Emi2, thereby creating a docking site for the Polo kinase. The Erp1/Emi2 phosphorylation by Polo kinase targets it to destruction, releasing APC/C from inhibition [110, 113, 114]. As a consequence, cyclin B is degraded, MPF activity is thus inactivated and the fertilized oocyte exits metaphase II. Given that Erp1/Emi2 can itself inhibit APC/C and stabilize MPF, why is the Mos/MEK/MAPK/p90Rsk required for metaphase II arrest? Recent works provided promising clues about the relationships between Mos and Erp1/Emi2. In Xenopus metaphase II-arrested oocytes, Erp1/Emi2 is a substrate of p90Rsk, and Mos-dependent phosphorylation of Erp1/Emi2 by p90Rsk is crucial for both stabilizing Erp1/Emi2 and establishing CSF arrest in meiosis II oocytes [115, 116]. More precisely, the Rsk-mediated phosphorylation of Erp1/Emi2 promotes its interaction with the protein phosphatase PP2A. PP2A dephosphorylates two distinct clusters of residues in Erp1/Emi2, one responsible for modulating its stability during the metaphase II-arrest and one controlling its binding to the APC/C [112, 117, 118]. Thus, Mos and Erp1/Emi2 collaboratively establish and maintain metaphase II arrest in Xenopus oocytes (Figure 3).


Mos in the oocyte: how to use MAPK independently of growth factors and transcription to control meiotic divisions.

Dupré A, Haccard O, Jessus C - J Signal Transduct (2010)

Meiotic arrest of the unfertilized oocyte: the downstream effectors of Mos/MAPK. In all species, oocytes halt meiosis to prevent embryonic development in the absence of fertilization. Depending on species, meiosis arrests at prophase I, metaphase I, metaphase II, or G1 following meiosis. Except in C. elegans, Mos was found to be the ubiquitous cytostatic factor responsible for the unfertilized oocyte arrest. Its downstream targets accounting for the meiotic arrest of the unfertilized oocytes are indicated.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3101788&req=5

fig3: Meiotic arrest of the unfertilized oocyte: the downstream effectors of Mos/MAPK. In all species, oocytes halt meiosis to prevent embryonic development in the absence of fertilization. Depending on species, meiosis arrests at prophase I, metaphase I, metaphase II, or G1 following meiosis. Except in C. elegans, Mos was found to be the ubiquitous cytostatic factor responsible for the unfertilized oocyte arrest. Its downstream targets accounting for the meiotic arrest of the unfertilized oocytes are indicated.
Mentions: In vertebrates, the Mos/MAPK pathway serves to stabilize MPF, ensuring an arrest at the metaphase stage. Releasing this blockage requires the activity of the APC/C protein complex, a ubiquitin ligase that targets cyclin B for destruction [108, 109]. In mouse and Xenopus metaphase II-arrested oocytes, APC/C is directly inhibited by the Erp1/Emi2 protein [110]. During oocyte maturation, Erp1/Emi2 appears only after metaphase I, explaining why the oocyte does not stop at metaphase I, but at metaphase II [111, 112]. Upon fertilization, a transient rise in free intracellular calcium activates calmodulin-dependent protein kinase II that phosphorylates Erp1/Emi2, thereby creating a docking site for the Polo kinase. The Erp1/Emi2 phosphorylation by Polo kinase targets it to destruction, releasing APC/C from inhibition [110, 113, 114]. As a consequence, cyclin B is degraded, MPF activity is thus inactivated and the fertilized oocyte exits metaphase II. Given that Erp1/Emi2 can itself inhibit APC/C and stabilize MPF, why is the Mos/MEK/MAPK/p90Rsk required for metaphase II arrest? Recent works provided promising clues about the relationships between Mos and Erp1/Emi2. In Xenopus metaphase II-arrested oocytes, Erp1/Emi2 is a substrate of p90Rsk, and Mos-dependent phosphorylation of Erp1/Emi2 by p90Rsk is crucial for both stabilizing Erp1/Emi2 and establishing CSF arrest in meiosis II oocytes [115, 116]. More precisely, the Rsk-mediated phosphorylation of Erp1/Emi2 promotes its interaction with the protein phosphatase PP2A. PP2A dephosphorylates two distinct clusters of residues in Erp1/Emi2, one responsible for modulating its stability during the metaphase II-arrest and one controlling its binding to the APC/C [112, 117, 118]. Thus, Mos and Erp1/Emi2 collaboratively establish and maintain metaphase II arrest in Xenopus oocytes (Figure 3).

Bottom Line: In one specific cell type however, the female germ cell, MAPK does not follow this canonical scheme.Which unique functions could explain the evolutionary cost to have selected one gene to only serve for few hours in one very specific cell type?This review discusses the original features of MAPK activation by Mos and the roles of this module in oocytes.

View Article: PubMed Central - PubMed

Affiliation: CNRS, UMR 7622-Biologie du Développement, 9 Quai Saint-Bernard, 75005 Paris, France.

ABSTRACT
In many cell types, the mitogen-activated protein kinase (MAPK) also named extracellular signal-regulated kinase (ERK) is activated in response to a variety of extracellular growth factor-receptor interactions and leads to the transcriptional activation of immediate early genes, hereby influencing a number of tissue-specific biological activities, as cell proliferation, survival and differentiation. In one specific cell type however, the female germ cell, MAPK does not follow this canonical scheme. In oocytes, MAPK is activated independently of growth factors and tyrosine kinase receptors, acts independently of transcriptional regulation, plays a crucial role in controlling meiotic divisions, and is under the control of a peculiar upstream regulator, the kinase Mos. Mos was originally identified as the transforming gene of Moloney murine sarcoma virus and its cellular homologue was the first proto-oncogene to be molecularly cloned. What could be the specific roles of Mos that render it necessary for meiosis? Which unique functions could explain the evolutionary cost to have selected one gene to only serve for few hours in one very specific cell type? This review discusses the original features of MAPK activation by Mos and the roles of this module in oocytes.

No MeSH data available.


Related in: MedlinePlus