title: Eph and NMDA receptors control Ca2+/calmodulin-dependent protein kinase II activation during C. elegans oocyte meiotic maturation.
abstract: Fertilization in the female reproductive tract depends on intercellular signaling mechanisms that coordinate sperm presence with oocyte meiotic progression. To achieve this coordination in Caenorhabditis elegans, sperm release an extracellular signal, the major sperm protein (MSP), to induce oocyte meiotic maturation and ovulation. MSP binds to multiple receptors, including the VAB-1 Eph receptor protein-tyrosine kinase on oocyte and ovarian sheath cell surfaces. Canonical VAB-1 ligands called ephrins negatively regulate oocyte maturation and MPK-1 mitogen-activated protein kinase (MAPK) activation. Here, we show that MSP and VAB-1 regulate the signaling properties of two Ca2+ channels that are encoded by the NMR-1 N-methyl D-aspartate type glutamate receptor subunit and ITR-1 inositol 1,4,5-triphosphate receptor. Ephrin/VAB-1 signaling acts upstream of ITR-1 to inhibit meiotic resumption, while NMR-1 prevents signaling by the UNC-43 Ca2+/calmodulin-dependent protein kinase II (CaMKII). MSP binding to VAB-1 stimulates NMR-1-dependent UNC-43 activation, and UNC-43 acts redundantly in oocytes to promote oocyte maturation and MAPK activation. Our results support a model in which VAB-1 switches from a negative regulator into a redundant positive regulator of oocyte maturation upon binding to MSP. NMR-1 mediates this switch by controlling UNC-43 CaMKII activation at the oocyte cortex.
authors.affiliation: Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Corrigan
authors.forename: Rajani
authors.initials: R
authors.lastname: Subramanian
authors.forename: Michael A
authors.initials: MA
authors.lastname: Miller
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation; D005260:Female; D015801:Helminth Proteins / Q000378:metabolism / Q000502:physiology; D008540:Meiosis; D009865:Oocytes / Q000254:growth & development*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D015801:Helminth Proteins; C436186:NMR-1 protein, C elegans; D016194:Receptors, N-Methyl-D-Aspartate; C050602:major sperm protein, nematode; D020794:Receptor Protein-Tyrosine Kinases; C111040:vab-1 protein, C elegans; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517679:unc-43 protein, C elegans