Vesicular traffic at the cell membrane regulates oocyte meiotic arrest

Wassim El-Jouni, Shirley Haun, Rawad Hodeify, Azida Hosein Walker, Khaled Machaca

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Vertebrate oocytes are maintained in meiotic arrest for prolonged periods of time before undergoing oocyte maturation in preparation for fertilization. Cyclic AMP (cAMP) signaling plays a crucial role in maintaining meiotic arrest, which is released by a species-specific hormonal signal. Evidence in both frog and mouse argues that meiotic arrest is maintained by a constitutively active G-protein coupled receptor (GPCR) leading to high cAMP levels. Because activated GPCRs are typically targeted for endocytosis as part of the signal desensitization pathway, we were interested in determining the role of trafficking at the cell membrane in maintaining meiotic arrest. Here we show that blocking exocytosis, using a dominant-negative SNAP25 mutant in Xenopus oocytes, releases meiotic arrest independently of progesterone. Oocyte maturation in response to the exocytic block induces the MAPK and Cdc25C signaling cascades, leading to MPF activation, germinal vesicle breakdown and arrest at metaphase of meiosis II with a normal bipolar spindle. It thus replicates all tested aspects of physiological maturation. Furthermore, inhibiting clathrin-mediated endocytosis hinders the effectiveness of progesterone in releasing meiotic arrest. These data show that vesicular traffic at the cell membrane is crucial in maintaining meiotic arrest in vertebrates, and support the argument for active recycling of a constitutively active GPCR at the cell membrane.

Original languageEnglish
Pages (from-to)3307-3315
Number of pages9
JournalDevelopment
Volume134
Issue number18
DOIs
Publication statusPublished - 1 Sep 2007

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Keywords

  • Clathrin
  • Endocytosis
  • Exocytosis
  • Meiotic arrest
  • Oocyte maturation
  • SNAP25
  • Xenopus laevis

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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