A Multifaceted Meiotic Response to MSP

Abstract

Miller et al. investigated the mechanisms by which major sperm protein (MSP) triggers oocyte maturation and ovulation in Caenorhabditis elegans . The authors identified the VAB-1 Eph receptor protein-tyrosine kinase (VAB-1) as an MSP receptor on both oocytes and smooth muscle-like gonadal sheath cells. Most oocytes arrest in meiotic prophase and resume meiosis after signals from sperm or nearby somatic cells that lead to activation of mitogen-activated protein kinase (MAPK) and cyclin-dependent kinase signaling pathways. The regulation of these pathways by cell surface signals, however, is poorly understood. Miller et al. used DNA microarray data together with RNA interference, C. elegans loss-of-function mutants, and an in situ binding assay to implicate VAB-1 in MSP-dependent oocyte maturation, ovulation, and activation of MAPK pathways. Ephrin-2 acted through VAB-1 to inhibit MAPK activation and oocyte maturation. MSP, which could bind to VAB-1 independently of its catalytic activity or ability to interact with ephrins, antagonized VAB-1 signaling on oocytes. MSP also promoted oocyte maturation by antagonizing a parallel VAB-1-independent inhibitory pathway mediated through sheath cells. MSP stimulated sheath cell contraction, which promotes ovulation, through VAB-1 independently of ephrin signaling. These data define a mechanism whereby MAPK signaling and oocyte maturation are inhibited in the absence of sperm; because MSP-domain proteins are found in many eukaryotic organisms, the data may also identify a widespread mechanism for regulating Eph receptor signaling. M. A. Miller, P. J. Ruest, M. Kosinski, S. K. Hanks, D. Greenstein, An Eph receptor sperm-sensing control mechanism for oocyte meiotic maturation in Caenorhabditis elegans . Genes Dev. 17 , 187-200 (2003). [Abstract] [Full Text]