Oocyte meiotic maturation is an essential biological process required for sexual reproduction. In C. elegans, the MSP hormone triggers meiotic maturation and MAP kinase (MAPK) activation in oocytes. In the absence of sperm, VAB-1 Eph/MSP receptor and sheath cell pathways inhibit meiotic maturation. MSP antagonizes these regulatory circuits to promote meiotic maturation and MAPK activation. A genetic screen for meiotic maturation defects defined the CGH-1 DEAD-box helicase as a negative regulator of MAPK activation in oocytes. In the wild type, MAPK is activated when sperm are present, whereas no MAPK activation is observed in proximal oocytes in females. By contrast, both
cgh-1 null and antimorphic (gf) mutations result in oocyte MAPK activation in female genetic backgrounds. In the presence of sperm, MAPK activation extends to distal oocytes, suggesting that
cgh-1 mutations affect the response threshold to the MSP signal. In addition,
cgh-1 has a cell non-autonomous function in inhibiting basal sheath cell contractions. CGH-1 localizes differently in the presence and absence of sperm. In the presence of sperm CGH-1 localizes to a subcortical band that encircles the oocyte; whereas, in the absence of sperm CGH-1 localizes to large aggregates in this subcortical region. In the
cgh-1(
ok492) null mutant, PGL-1, MEX-3, OMA-2, and AIR-2 localize abnormally to large filamentous aggregates in oocytes. Interestingly, CGH-1 protein itself forms filamentous aggregates in the
cgh-1(
tn691gf) antimorph. CGH-1 may function in the remodeling of RNP complexes, as proposed for other DExH/D helicases. In a bioinformatic screen for proteins predicted to contain MAPK docking sites (S. Arur et al., this meeting), CGH-1 was found to possess three D-domains and one FXFP-motif and two potential S/TP phosphorylation sites at S67 and T168. In vitro kinetic data suggest that S67 is the primary phosphorylation site for mammalian ERK2. In vivo data indicate that CGH-1 is phosphorylated on serine and that phosphorylation is eliminated in
mpk-1(
ga117) null and
cgh-1(
tn691gf) at the non-permissive temperature. Interestingly, the
cgh-1(
tn691gf) mutation results from a P68L substitution at the phosporylation site in the Q-motif. The Q-motif of DEAD-box helicases regulates ATP binding and hydrolysis, and affinity for RNA substrates. Our current hypothesis is that CGH-1 phosphorylation by MAPK controls a positive feedback loop for MAPK activation.