An Eph receptor sperm-sensing control mechanism for oocyte meiotic maturation inCaenorhabditis elegans

Abstract

During sexual reproduction in most animals, oocytes arrest in meiotic prophase and resume meiosis (meiotic maturation) in response to sperm or somatic cell signals. Despite progress in delineating mitogen-activated protein kinase (MAPK) and CDK/cyclin activation pathways involved in meiotic maturation, it is less clear how these pathways are regulated at the cell surface. The Caenorhabditis elegans major sperm protein (MSP) signals oocytes, which are arrested in meiotic prophase, to resume meiosis and ovulate. We used DNA microarray data and an in situ binding assay to identify the VAB-1 Eph receptor protein-tyrosine kinase as an MSP receptor. We show that VAB-1 and a somatic gonadal sheath cell-dependent pathway, defined by the CEH-18 POU-class homeoprotein, negatively regulate meiotic maturation and MAPK activation. MSP antagonizes these inhibitory signaling circuits, in part by binding VAB-1 on oocytes and sheath cells. Our results define a sperm-sensing control mechanism that inhibits oocyte maturation, MAPK activation, and ovulation when sperm are unavailable for fertilization. MSP-domain proteins are found in diverse animal taxa, where they may regulate contact-dependent Eph receptor signaling pathways. Sexual reproduction requires meiosis to generate haploid (1n) gamete nuclei, which unite after fertilization to form the diploid (2n) totipotent embryo. Despite this universal requirement, meiosis is regulated differently in sperm and oocytes. Whereas sperm proceed through the meiotic divisions uninterrupted, oocytes almost invariably arrest during one, and sometimes two stages following premeiotic DNA replication and meiotic recombination, depending on the species. Therefore, the completion of meiosis in oocytes must be coordinated with development and fertilization to ensure successful reproduction. To achieve this coordination, sperm and somatic cell signals regulate oocyte meiotic progression by activating downstream cyclin-dependent kinase regulatory pathways, which mediate cell cycle transitions in eukaryotes (for review, see Ferrell 1999; Masui 2001).The oocytes of most animals, including the early-diverging sponges and cnidarians (Masui 1985), arrest during meiotic prophase, suggesting that this regulatory mechanism represents a fundamental metazoan reproductive strategy. Human oocytes can remain arrested in prophase for several decades, and aberrant regulation of the first meiotic division is a major cause of infertility, miscarriage, and chromosomal nondisjunction (for review, see Jacobs 1992; Hunt and LeMaire-Adkins 1998). In most animals examined, meiosis resumes in response to nonautonomous signals through a process termed meiotic maturation, which prepares the oocyte for fertilization and embryogenesis. The hallmarks of meiotic maturation include nuclear envelope breakdown, cortical cytoskeletal rearrangement, and meiotic spindle assembly. Studies of Xenopus have identified two key intracellular enzymes, maturation-promoting factor (MPF), a complex consisting of the regulatory protein cyclin B...

Profiling of gender-regulated gene transcripts in the filarial nematode Brugia malayi by cDNA oligonucleotide array analysis

“…MSPs are involved in the movement of the amoeboid nematode sperm [32]. Recent studies show that MSPs also have a signaling role in oocyte production and maturation in C. elegans [33,34]. The retention of this MSP signaling function in Ascaris suum [34] suggests that this may also be present in filarial nematodes.…”

“…Recent studies show that MSPs also have a signaling role in oocyte production and maturation in C. elegans [33,34]. The retention of this MSP signaling function in Ascaris suum [34] suggests that this may also be present in filarial nematodes. Thus, the finding that 20% of highly male-up-regulated clusters in our study were either MSPs or homologues of C. elegans genes that contain an MSP domain is impressive but not surprising (Table 2).…”

Structural components of the nonstriated contractile apparatuses in the Caenorhabditis elegans gonadal myoepithelial sheath and their essential roles for ovulation

“…Contraction of the myoepithelial sheath is periodically enhanced upon maturation of the most proximal oocytes (McCarter et al, 1997(McCarter et al, , 1999. Sheath contraction is negatively regulated by ceh-18 encoding a POU-class homeoprotein (Rose et al, 1997;Miller et al, 2003) and gap junctions that are formed between the myoepithelial sheath and maturing oocytes (Whitten and Miller, 2006). On the other hand, it is enhanced by major sperm protein (Miller et al, 2001;Kosinski et al, 2005) by means of the VAB-1 Eph receptor (Miller et al, 2003).…”

“…Sheath contraction is negatively regulated by ceh-18 encoding a POU-class homeoprotein (Rose et al, 1997;Miller et al, 2003) and gap junctions that are formed between the myoepithelial sheath and maturing oocytes (Whitten and Miller, 2006). On the other hand, it is enhanced by major sperm protein (Miller et al, 2001;Kosinski et al, 2005) by means of the VAB-1 Eph receptor (Miller et al, 2003). In addition, NMR-1 NMDA receptor and UNC-43 Ca 2ϩ -calmodulin-dependent kinase II negatively regulate sperm-dependent sheath contraction (Corrigan et al, 2005), whereas ITR-1 inositol triphosphate receptor (Yin et al, 2004), VAV-1 Rho/Rac guanine nucleotide exchange factor (GEF), and RHO-1 small GTPase (Norman et al, 2005) enhance contraction.…”

Communication between oocytes and somatic cells regulates volatile pheromone production in Caenorhabditis elegans

“…Both self-sperm and nonself-sperm secrete protein ligands, known as major sperm proteins (MSPs), that activate signal transduction pathways in both unfertilized oocytes, leading to activation of mitogen-activated protein kinase (MPK-1), and the somatic gonad, involving transcription factor CEH-18. The result of this signaling is the release of oocytes from prophase I arrest and the ovulation of unarrested oocytes into the uterus (3,4).…”