Regulation of olfactory receptor expression by a serine-threonine kinase. The ability to sense chemical cues in the environment is crucial for C. elegans to find food, avoid harm, and choose an appropriate developmental program. Initial contact with these cues occurs via G-protein coupled odorant receptors localized in the cilia of sensory neurons. Distinct sensory neurons play highly specialized sensory roles. Therefore, specific receptors must be expressed within the correct neuron and at the correct level to enable the worm to interpret the cue correctly and thus initiate the proper behavioral response. This is a remarkable feat given the complex and constantly changing environment. Very little is known in any organism about how olfactory receptor expression is regulated, and how sensory information is integrated to modulate behavior and development. We describe the gene
sns-8 , a kinase required to regulate expression of a subset of odorant receptors.
sns-8 was isolated from genetic screens to find factors that affect expression of the odorant receptor,
str-1 .
str-1 expression is dramatically reduced in
sns-8 mutants. We investigated the extent of olfactory receptor expression defects, and found that a subset of receptors expressed in the AWB olfactory neurons and a receptor expressed in the ASH polymodal neurons require SNS-8 function. In addition to having defects in the regulation of olfactory receptor expression,
sns-8 mutants are small (see abstract by Meduzia et al.) and are developmentally delayed.
sns-8 encodes a serine-threonine kinase closely related to PAR-1. It is broadly expressed throughout the nervous system and is cytoplasmically localized. SNS-8 is required neuronally to rescue its body size defects - adding
sns-8 to an ever-increasing group of genes that implicate neuronal, and perhaps sensory, activity in the regulation of body size (see abstract by Fujiwara et al). We have found that expression of SNS-8 specifically in the AWB neurons restores
str-1 expression - indicating that SNS-8 acts cell autonomously to regulate receptor expression. We have evidence indicating
sns-8 mutants have compromised sensory signaling.
sns-8 worms show a weakened ability to assess correct dauer inducing conditions.
sns-8 mutants show a synthetic dauer constitutive phenotype (Syn-Daf) with other genes known to regulate sensory inputs into the dauer pathway. These genes include
egl-4 and
tph-1 .
egl-4 mutants have numerous characterized sensory defects and has been shown to function in the Group II TGF-ß signaling pathway for dauer formation (Daniels et al, 2000).
egl-4 encodes a cGMP-dependant kinase (see abstract by Fujiwara et al). While neither
sns-8 nor
egl-4 mutants alone form dauers at 20ûC, we have shown that
sns-8;
egl-4 double mutants inappropriately form dauers at this temperature. Surprisingly, we have found that
egl-4 mutants also show defective
str-1 expression, perhaps indicating a previously undescribed role for
egl-4 in the regulation of expression of a subset of receptors. In addition, we find that when
sns-8 is combined with a mutant that knocks out serotonin synthesis,
tph-1 (Sze et al. 2000), these doubles also show a Syn-Daf interaction at 20ûC. We therefore propose a model in which
sns-8 regulates sensory inputs into the TGF- ß dauer regulatory pathway by regulating the expression of a subset of olfactory receptors.