Signalling pathways controlling the initiation of Xenopus oocyte maturation.

Abstract

Xenopus laevis oocytes are physiologically arrested at the first meiotic prophase. Re-initiation of meiosis, or oocyte maturation, is triggered in vivo by progesterone, but can also be triggered by insulin and insulin-like growth factor-1 (IGF-1) in vitro. The mechanism by which these two very different hormones regulate the same physiological process is poorly understood. Chapter 2 describes my research that contributed to the characterization of the progesterone receptor responsible for inducing oocyte maturation. We demonstrated that the Xenopus progesterone receptor (xPR) is a dual functional protein. When expressed in the heterologous COS-7 cells, OR is imported into the nucleus and functions as a progesterone-regulated transcription factor. In contrast, the endogenous OR in Xenopus oocytes is restricted in the cytoplasm and appears to mediate cytoplasmic signalling. Chapter 3 describes a functional link between the IGF-1 receptor and G-protein signalling in the control of oocyte maturation. The Xenopus homologue of GIPC, a PDZ-domain-containing protein, was identified as a binding partner for the cytoplasmic domain of the IGF-1 receptor. GIPC is known to interact with the C-terminus of a Galphai-specific GAP, RGS-GAIP. Expression of two dominant negative forms of xGIPC blocked insulin-induced MAPK activation and oocyte maturation, while full-length xGIPC synergized with human RGS-GRIP to enhance insulin signalling. This is the first demonstration that the GIPC/RGS-GAIP complex acts positively in IGF-1 receptor signalling.