DOC1R: a MAP kinase substrate that control microtubule organization of metaphase II mouse oocytes.
For the success of fertilization, spindles of vertebrate oocytes must remain stable and correctly organized during the arrest in metaphase II of meiosis. Using a two-hybrid screen with MAPK as a bait, we have recently identified MISS (MAPK interacting and spindle stabilizing) which controls mouse oocyte metaphase II spindle stability. Using the same screen, we identify another MAPK partner, DOC1R (Deleted in oral cancer one related), a murine homologue of a potential human tumor suppressor gene. We characterize DOC1R during mouse oocyte meiosis resumption. DOC1R is regulated by phosphorylation during meiotic maturation by MPF (M-phase promoting factor) and by the MOS/./MAPK pathway. DOC1R and a DOC1R-GFP fusion localize to microtubules during meiotic maturation. Consistent with this microtubular localization, we show, by antisense and double-stranded RNA injection, that depletion of DOC1R induces microtubule defects in metaphase II oocytes. These defects are rescued by overexpressing a Xenopus DOC1R, showing that they are specific to DOC1R. Thus, the discovery of DOC1R, a substrate of MAPK that regulates microtubule organization of metaphase II mouse oocytes, reinforces the importance of this pathway in the control of spindle stability during the metaphase II arrest.
Terret
M Emilie
ME
UMR 7622, CNRS, Université Paris VI, 9 quai Saint Bernard, Bat. C, 75252 Paris, cedex 05, France.
Lefebvre
Christophe
C
Djiane
Alexandre
A
Rassinier
Pascale
P
Moreau
Jacques
J
Maro
Bernard
B
Verlhac
Marie-Helene
MH
D000595:Amino Acid Sequence; D000818:Animals; D019926:Cyclin B / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D006801:Humans; D008540:Meiosis / Q000502:physiology*; D000090204:Mesothelin; D008677:Metaphase / Q000502:physiology*; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000502:physiology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D008941:Spindle Apparatus / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D014982:Xenopus laevis
C401561:CDK2AP2 protein, human; D019926:Cyclin B; C485718:Doc-1r protein, mouse; C000715528:Msln protein, mouse; D015513:Oncogene Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D020928:Mitogen-Activated Protein Kinases; D000090204:Mesothelin