Program of the 2001 International Worm Meeting - Sternberg Lab ...

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406. Activity-dependent transcription
in the AWA sensory neuron: the roles
of osm-9, ky440, and other
transduction molecules
Amanda Kahn 1,2 , David Tobin 2 ,
Cori Bargmann 2
1 email: amandak@phy.ucsf.edu
2 HHMI and UCSF, 513 Parnassus Ave, Rm
S-1471, San Francisco, CA 94143-0452
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
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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.