Vesicular Trafficking in Meiotic Arrest

Science's STKE  04 Sep 2007:
Vol. 2007, Issue 402, pp. tw319
DOI: 10.1126/stke.4022007tw319

A constitutively active G protein-coupled receptor (GPCR) resulting in the production of adenosine 3',5'-monophosphate (cAMP) has been implicated in maintaining meiotic arrest. El-Jouni et al. investigated whether vesicular trafficking at the plasma membrane may be involved in this process. Using Xenopus oocytes, they inhibited exocytosis with a dominant-negative form of SNAP25 (a protein that functions as a critical component of the SNARE machinery that allows vesicles to fuse with the plasma membrane) and found that the oocytes were released from meiotic arrest in the absence of hormonal stimulation (progesterone). Membrane capacitance was monitored as an indicator of exocytosis. Forskolin, which directly activates adenylyl cyclase in the absence of receptor stimulation, and cholera toxin, which activates Gαs proteins, prevented progesterone and the dominant-negative SNAP25 from triggering maturation, suggesting that these two agents act upstream of adenylyl cyclase and Gαs. Oocytes have constitutive endocytosis as well as clathrin-mediated endocytosis. Blocking constitutive endocytosis had no effect on oocyte maturation, whereas blocking clathrin-mediated endocytosis with monodansylcadaverine delayed progesterone-mediated oocyte maturation. Thus, membrane trafficking, which presumably includes internalization and recycling of the GPCR, may contribute to the receptor’s constitutive activity. Inhibiting exocytosis may be one mechanism that contributes to the maturation process. A role for a block in exocytosis in Xenopus is consistent with the morphological changes and decrease in surface area associated with maturation. It will be interesting to understand how the physiological stimuli that trigger maturation are connected to changes in vesicular traffic.

W. El-Jouni, S. Haun, R. Hodeify, A. H. Walker, K. Machaca, Vesicular traffic at the cell membrane regulates oocyte meiotic arrest. Development 134, 3307-3315 (2007). [PubMed]