With prolonged exposure to an odorant, C. elegans exhibit a diminished response to the odorant. In the early adaptation assay which we have previously developed, the response to an odorant diminishes with only 5 minutes of exposure to the odorant. Early adaptation depends on the function of the interneuron AIY and the activity of the Ras-MAPK pathway. To elucidate the mechanisms of early adaptation, we screened for mutants that show defects in this assay, and isolated 26 mutant strains. We identified two of the mutants as alleles of
gpc-1(
pe372) and
nep-2(
pe356).
gpc-1 encodes a G protein <font face=symbol>g</font> subunit. Previous studies have shown that
gpc-1 is expressed in the sensory neurons, strongly in ADL, ASH, ASJ, and faintly in AFD, ASI and AWB, and acts in multiple sensory neurons for gustatory plasticity. In addition to the neurons listed above, we detected the expression of
gpc-1 in AWC sensory neurons, which mainly sense the odorant benzaldehyde used in our assay. Furthermore, expression of
gpc-1 in AWC sensory neurons sufficiently rescues the defect of
gpc-1 mutants in early adaptation.
nep-2 encodes one of the neprilysin homologs in C. elegans. Neprilysin is a membrane protein with a large extracellular domain having endopeptidase activity.
nep-2 was previously reported to be expressed in body wall muscles. In addition to body wall muscles, we find its expression in several neurons, including AIMs and SMBs. Expression of
nep-2 cDNA in several combinations of interneurons fully rescues the defect, and expression in body wall muscles also partially rescues the defect. This suggests that NEP-2 acts cell nonautonomously. Furthermore, by using a heat-shock promoter, we confirmed that expression of
nep-2 at the time of the assay is sufficient for the rescue. Therefore, the early adaptation defect of
nep-2 mutant is not due to developmental abnormality. The HExxH motif is well conserved among neprilysin homologs, and is required for retention of zinc ion at peptidase active center. NEP-2 also has this motif, and when it is substituted to FExxF, the
nep-2 cDNA lose its ability to rescue the defect. Therefore, similar to other neprilysin homologs, NEP-2 appears to act for degradation of extracellular peptides. This speculation also suggests that peptide signaling is important for early adaptation. We are currently conducting a screen for such peptides.