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The Journal of Neuroscience, October 4, 2006, 26(40):10082-10090; doi:10.1523/JNEUROSCI.0819-06.2006

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Cellular/Molecular
Starvation Induces cAMP Response Element-Binding Protein-Dependent Gene Expression through Octopamine–Gq Signaling in Caenorhabditis elegans

Satoshi Suo,1 Yoshishige Kimura,2 and Hubert H. M. Van Tol1 {dagger}

1Departments of Psychiatry, Pharmacology, and Physiology, Institute of Medical Science, University of Toronto and Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8, and 2Department of Medical Genetics, University of Toronto and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5

Correspondence should be addressed to Dr. Satoshi Suo, Laboratory of Molecular Neurobiology, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8. Email: satoshi.suo{at}utoronto.ca

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{alpha}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{alpha}q ortholog EGL-30 (egg-laying defective family member 30). The signaling cascade is only partially dependent on the phospholipase Cbeta (EGL-8) and is negatively regulated by G{alpha}o [GOA-1 (G-protein, O, {alpha} 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{alpha}q.

Key words: aminergic; C. elegans; CREB; GPCR; Gq; octopamine; starvation


Received Feb. 22, 2006; revised July 13, 2006; accepted Aug. 20, 2006.

Correspondence should be addressed to Dr. Satoshi Suo, Laboratory of Molecular Neurobiology, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8. Email: satoshi.suo{at}utoronto.ca




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