Amine neurotransmitters are capable of activating the transcription factor cAMP response element binding protein (CREB). The subsequent activation of CRE-dependent gene expression has been shown to function in a broad range of biological processes. In C. elegans, the CRE-dependent gene expression can be visualized using a transgenic strain carrying a transcriptional reporter in which CRE is fused to a GFP reporter (cre::gfp). GFP expression in this strain is dependent on the
crh-1 gene that encodes a CREB homologue (ref.1). Using the cre::gfp reporter strain, we examined the effect of amine neurotransmitters on the CRE-dependent gene expression in C. elegans. Exogenous application of octopamine to animals carrying cre::gfp induced GFP expression in SMB neurons. The SMB neurons are a postsynaptic target for the octopaminergic RIC neurons. The
ser-3 gene encodes a putative G protein-coupled receptor that is highly homologous to the Gq-coupled octopamine receptor OAMB identified in Drosophila and Apis. Using a
ser-3 deletion mutant we show that
ser-3 is required for the octopamine-induced GFP expression. Furthermore,
ser-3 promoter-GFP fusion constructs mediate GFP expression in various cells including SMB neurons. In addition,
crh-1 and
egl-30, encoding the subunit of Gq, are also required for the response to octopamine.Since exogenous octopamine is known to phenocopy starvation in C. elegans, we tested the effect of starvation on cre::gfp expression and found that this also induced GFP expression in SMB neurons. A deletion mutant for the
tbh-1 gene, encoding a tyramine--hydroxylase that is required for octopamine synthesis, lost the response to starvation but not to exogenously applied octopamine. The mutants for
ser-3,
egl-30, and
crh-1 also had blunted response to starvation. In addition, octopamine treatment or starvation in the presence of serotonin resulted in a reduced number of animals with GFP expression in SMB neurons.Our results suggest that starvation mediates octopamine release and activate
ser-3,
egl-30, and
crh-1 signaling cascade to induce CRE-dependent gene expression in SMB neurons. This signal can be inhibited by serotonin.ref.1 Kimura et. al. 2002. EMBO rep. 3, 962-966. We thank Dr Kimura, Dr Avery, and CGC for strains, Ms Ordog for technical assistance, and Dr Culotti for valuable discussions. SS is a recipient of CAMH fellowship. This work is supported by CPRF/Astra-Zeneca/CIHR. HVT is a holder of a Canadian Research Chair in Neurobiology.