A network of stimulatory and inhibitory Galpha-subunits regulates olfaction in Caenorhabditis elegans.
The two pairs of sensory neurons of C. elegans, AWA and AWC, that mediate odorant attraction, express six Galpha-subunits, suggesting that olfaction is regulated by a complex signaling network. Here, we describe the cellular localization and functions of the six olfactory Galpha-subunits: GPA-2, GPA-3, GPA-5, GPA-6, GPA-13, and ODR-3. All except GPA-6 localize to sensory cilia, suggesting a direct role in sensory transduction. GPA-2, GPA-3, GPA-5, and GPA-6 are also present in cell bodies and axons and GPA-5 specifically localizes to synaptic sites. Analysis of animals with single- to sixfold loss-of-function mutations shows that olfaction involves a balance between multiple stimulatory and inhibitory signals. ODR-3 constitutes the main stimulatory signal and is sufficient for the detection of odorants. GPA-3 forms a second stimulatory signal in the AWA and AWC neurons, also sufficient for odorant detection. In AWA, signaling is suppressed by GPA-5. In AWC, GPA-2 and GPA-13 negatively and positively regulate signaling, respectively. Finally, we show that only ODR-3 plays a role in cilia morphogenesis. Defects in this process are, however, independent of olfactory behavior. Our findings reveal the existence of a complex signaling network that controls odorant detection by C. elegans.
Lans
Hannes
H
MGC Department of Cell Biology and Genetics, Center for Biomedical Genetics, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands.
Rademakers
Suzanne
S
Jansen
Gert
G
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D009812:Odorants; D010957:Plasmids / Q000235:genetics; D012903:Smell / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D044385:GTP-Binding Protein alpha Subunits