osm-9 encodes a predicted cation channel that is involved in multiple C. elegans sensory modalities. Loss of
osm-9 function eliminates chemotaxis to the AWA-sensed odorant diacetyl, compromises adaptation to a subset of AWC-sensed odorants, and diminishes avoidance of ASH-sensed noxious stimuli.
osm-9 mutants also exhibit reduced AWA expression of a Green Fluorescent Protein (GFP) transgene driven by the promoter of the diacetyl receptor, ODR-10. OSM-9 is similar to sensory channels in other species, including the TRP channels and the mammalian capsaicin receptor VR-1. We are characterizing
osm-9 and related genes to learn more about the regulation and function of this novel channel family. In a forward genetic screen, we used the activity-dependent regulation of
odr-10 ::GFP as an assay to identify additional genes that affect OSM-9 signaling.
ky440 was isolated in a screen for dominant suppressors of the reduced
odr-10:: GFP expression in
osm-9 mutants.
ky440 restores
odr-10:: GFP expression in an
osm-9 (
n2743) background (where the channel is present, but mislocalized) or in an
osm-9 null mutant. OSM-9 belongs to a family of C. elegans channels, and both OSM-9 and the related channel OCR-2 are expressed in AWA neurons. The
osm-9 ky440 ocr-2 triple mutant does not exhibit expression of
odr-10:: GFP. These results suggest a model whereby
ky440 enhances a low level of channel activity to allow for
odr-10 ::GFP expression, but that some level of activity through this channel family is required for this suppression. Recent progress in snip-SNP mapping of
ky440 and another mutant,
ky456 , will be presented. We have also taken a candidate approach to studying
osm-9 signaling, using existing C. elegans signaling mutants. The involvement of
osm-9 in olfaction suggests that it is activated by a G-protein signaling pathway. Animals doubly mutant for the olfactory G protein genes
odr-3 and
gpa-3 have a defect in
odr-10 ::GFP expression similar to that of
osm-9 mutants. Our results suggest that the G alpha proteins
odr-3 and
gpa-3 play redundant roles in the regulation of
odr-10: : GFP. We suggest that the activation of G-protein coupled receptors stimulates ODR-3 and GPA-3, which in turn activate OSM-9/OCR-2. Channel activity impinges upon transcriptional control of
odr-10 , as well as the behavior of the animal. We hope to clone
ky440 and
ky456 , and understand their roles within the AWA transcriptional and behavioral pathways.