DOC1R: a MAP kinase substrate that control microtubule organization of metaphase II mouse oocytes

Marie-Emilie Terret (1) , Christophe Lefebvre (2) , Alexandre Djiane (3) , Pascale Rassinier (1) , Jacques Moreau (4, 5) , Bernard Maro (1) , Marie-Hélène Verlhac (6, 1)

1 LBD - Laboratoire de Biologie du Développement
2 NA - Neuroimmunologie des annélides
3 IRCM - U896 Inserm - UM1 - Institut de recherche en cancérologie de Montpellier
4 ENSAT - École nationale supérieure agronomique de Toulouse
5 IJM (UMR_7592) - Institut Jacques Monod
6 CIRB - Centre interdisciplinaire de recherche en biologie

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.

Mots clés: DOC1R; MAPK; Mouse meiotic maturation; Microtubules

Domaines: Sciences du Vivant [q-bio]

Marie-Emilie Terret, Christophe Lefebvre, Alexandre Djiane, Pascale Rassinier, Jacques Moreau, et al.. DOC1R: a MAP kinase substrate that control microtubule organization of metaphase II mouse oocytes. Development (Cambridge, England), 2003, 130 (21), pp.5169-5177. ⟨10.1242/dev.00731⟩. ⟨hal-02107207⟩