Traffic Control for Oocytes

Abstract

The nematode C. elegans , not wanting to waste its resources, produces mature oocytes through meiotic maturation only when the presence of sperm is detected. The detection system consists of a transmembrane receptor protein, VAB-1, which recognizes a secreted sperm protein known as MSP (major sperm protein). Constitutive signaling through VAB-1 appears to hold oocytes in check, and the signal from sperm decreases such signaling to allow the oocyte to mature. VAB-1 occurs on both the oocytes themselves and gonadal sheath cells. Cheng et al . used a fusion protein of green fluorescent protein (GFP) linked to VAB-1 to monitor the receptor’s location and report that regulation of endocytic trafficking of the receptor might provide a critical control point for the regulation of oocyte maturation. In the absence of sperm, VAB-1::GFP was localized with a marker of recycling endosomes at the cortex. In hermaphrodites (which make their own sperm), VAB-1 was found instead in larger cytoplasmic vesicles. In a mutant in which vesicle transport from the recycling compartment to the plasma membrane is inhibited, VAB-1::GFP accumulated in the endocytic recycling compartment and maturation was inhibited. A search for proteins that interacted with the intracellular domain of VAB-1 yielded RAN-1, which was previously genetically identified as a negative regulator of oocyte maturation but is better known for its role in controlling nuclear transport. Depletion of RAN-1 with RNAi reduced the abundance of VAB-1::GFP in the cortex and enhanced accumulation in the larger cytoplasmic vesicles. The sheath cells do their part through signaling that requires a heterotrimeric guanine nucleotide-binding protein (G protein) and gap-junction channels. Disruption of these elements with RNAi appeared to diminish the signals required to inhibit maturation in the absence of sperm and led exclusion of VAB-1::GFP from the recycling endosome compartment. Although cause and effect remain to be formally established, the authors propose that the gonadal sheath cells may have a primary role in sensing MSP and then influence trafficking in the oocyte and, thus, its ability to respond directly to MSP. As Hang et al . note in commentary, why the double layer of regulation is required and exactly how VAB-1 trafficking regulates signaling by the receptor are among a series of new directions for study that are brought into focus by the new results. H. Cheng, J. A. Govindan, D. Greenstein, Regulated trafficking of the MSP/Eph receptor during oocyte meiotic maturation in C. elegans . Curr. Biol. 18 , 705-714 (2008). [PubMed] J. S. Hang, B. D. Grant, A. Singson, Meiotic maturation: Receptor trafficking is the key. Curr. Biol. 18 , R416-R418 (2008). [PubMed]