Role for endocytosis of a constitutively active GPCR (GPR185) in releasing vertebrate oocyte meiotic arrest

Nancy Nader, Maya Dib, Arwa Daalis, Rashmi P. Kulkarni, Khaled Machaca

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Vertebrate oocytes are naturally arrested at prophase of meiosis I for sustained periods of time before resuming meiosis in a process called oocyte maturation that prepares the egg for fertilization. Members of the constitutively active GPR3/6/12 family of G-protein coupled receptors represent important mediators of meiotic arrest. In the frog oocyte the GPR3/12 homolog GPRx (renamed GPR185) has been shown to sustain meiotic arrest by increasing intracellular cAMP levels through GαSβγ. Here we show that GPRx is enriched at the cell membrane (~80%), recycles through an endosomal compartment at steady state, and loses its ability to signal once trapped intracellularly. Progesterone-mediated oocyte maturation is associated with significant internalization of both endogenous and overexpressed GPRx. Furthermore, a GPRx mutant that does not internalize in response to progesterone is significantly more efficient than wild-type GPRx at blocking oocyte maturation. Collectively our results argue that internalization of the constitutively active GPRx is important to release oocyte meiotic arrest.

Original languageEnglish
Pages (from-to)355-366
Number of pages12
JournalDevelopmental Biology
Volume395
Issue number2
DOIs
Publication statusPublished - 15 Nov 2014

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Keywords

  • CAMP
  • Constitutive
  • G-protein coupled receptor
  • GPR185
  • GPRx
  • Internalization
  • Meiotic arrest
  • Oocyte maturation
  • Trafficking
  • Xenopus laevis

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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