Starvation Induces cAMP Response Element-Binding Protein-Dependent Gene Expression through Octopamine–G_qSignaling inCaenorhabditis elegans

Abstract

The nervous system plays a critical role in adaptation to a new environment. In Caenorhabditis elegans, reduced access to food requires both changes in behavior as well as metabolic adaptation for survival, which is postulated to involve the bioamine octopamine. The transcription factor cAMP response element-binding protein (CREB) is generally activated by G-protein-coupled receptors (GPCRs) that activate G␣ s and is known to play an important role in long-term changes, including synaptic plasticity. We show that, in C. elegans, the CREB ortholog CRH-1 (CREB homolog family member 1) activates in vivo a cAMP response element-green fluorescent protein fusion reporter in a subset of neurons during starvation. This starvation response is mediated by octopamine via the GPCR SER-3 (serotonin/ octopamine receptor family member 3) and is fully dependent on the subsequent activation of the G␣q ortholog EGL-30 (egg-laying defective family member 30). The signaling cascade is only partially dependent on the phospholipase C␤ (EGL-8) and is negatively regulated by G␣ o [GOA-1 (G-protein, O, ␣ subunit family member 1)] and calcium/calmodulin-dependent kinase [UNC-43 (uncoordinated family member 43)]. Nonstarved animals in a liquid environment mediate a similar response that is octopamine independent. The results show that the endogenous octopamine system in C. elegans is activated by starvation and that different environmental stimuli can activate CREB through G␣ q .Key words: aminergic; C. elegans; CREB; GPCR; G q ; octopamine; starvation Introduction cAMP response element-binding protein (CREB) is a signalactivated transcription factor that, after phosphorylation, induces expression of genes from promoters containing the cAMPresponse element (CRE) enhancer (Mayr and Montminy, 2001). CREB is activated by various physiological stimuli and plays important roles in many biological processes (Lonze and Ginty, 2002;Johannessen et al., 2004). The bioamine neurotransmitters dopamine, serotonin, and norepinephrine can activate CREB (Hyman, 1996;Mayford and Kandel, 1999;Simonneaux and Ribelayga, 2003). Most studies show that bioamine-induced CREB activation is dependent on G␣ s -coupled bioamine receptors through an adenylyl cyclase-protein kinase A (PKA) signaling pathway. However, little is known about in vivo mechanisms and the possible involvement of alternative cascades leading to CREB activation. Some in vitro studies suggest that G␣ q can activate CREB (Lin et al., 1998;Chalecka-Franaszek et al., 1999;Thonberg et al., 2002), although it is unknown whether the G␣ q -CREB pathway is of physiological relevance.Caenorhabditis elegans is a model organism that is particularly suitable for genetic studies. The bioamines dopamine (Sulston et al., 1975), serotonin (Horvitz et al., 1982), tyramine (Alkema et al., 2005), and octopamine (Horvitz et al., 1982) have been found in C. elegans and are believed to function as both neurotransmitters as well as neurohumoral factors. Octopamine is considered to be the invertebrate biological equiv...

Regulation of Serotonin Biosynthesis by the G Proteins Gαo and Gαq Controls Serotonin Signaling inCaenorhabditis elegans

“…A transcription factor re-quired for tph-1 expression in the HSNs, UNC-86, has been identified (Sze et al 2002) and is thus a possible target of Ga o /Ga q signaling. The regulation might also occur through the CREB transcription factor, since Ga o /Ga q signaling can control expression of an artificial reporter gene regulated by CREB (Suo et al 2006). Regardless of the specific mechanism, our results show that Ga o /Ga q regulate egg laying in part through control of tph-1 transcription and suggest that the G proteins may more widely regulate neural gene expression to have their antagonistic effects on neural function.…”

Tyramine and Octopamine Independently Inhibit Serotonin-Stimulated Aversive Behaviors inCaenorhabditis elegansthrough Two Novel Amine Receptors

“…TA and OA act through separate receptors to abolish 5-HTdependent increases in responsiveness to dilute octanol Two C. elegans G␣ o -coupled TA receptors (SER-2, TYRA-2) and a predicted G␣ q -coupled OA receptor (SER-3) have been described previously Rex et al, 2005;Suo et al, 2006). To determine whether these TA/OA receptors were involved in the TA/OA effects on octanol sensitivity described above, ser-2(pk1357), tyra-2(tm1846), and ser-3(ad1774) null animals were examined for the aminergic sensitivity of their responses to dilute octanol.…”

Trace amine-associated receptor 1—Family archetype or iconoclast?

“…Furthermore, pharmacologic manipulations (Borison et al, 1974;Borison et al, 1975;Boulton, 1976a;Philips & Boulton, 1979;Stoff et al, 1984;Boulton et al, 1990;Juorio et al 1991a;Juorio et al 1991b) and lesioning studies Juorio & Jones, 1981;Greenshaw et al, 1985;Greenshaw et al, 1986;Greenshaw et al, 1986;Juorio et al, 1987; can significantly influence TA turnover and levels with physiological (Becu-Villalobos, 1987;Cheng, 1990;Hirashima, 1999;Lee et al, 2003) and behavioral (Dourish, 1982;Lapin, 1996;Rex et al, 2004;Suo et al, 2006) consequences.…”