title: Control of Neuropeptide Expression by Parallel Activity-dependent Pathways in Caenorhabditis elegans.
abstract: Monitoring of neuronal activity within circuits facilitates integrated responses and rapid changes in behavior. We have identified a system in Caenorhabditis elegans where neuropeptide expression is dependent on the ability of the BAG neurons to sense carbon dioxide. In C. elegans, CO2sensing is predominantly coordinated by the BAG-expressed receptor-type guanylate cyclase GCY-9. GCY-9 binding to CO2causes accumulation of cyclic GMP and opening of the cGMP-gated TAX-2/TAX-4 cation channels; provoking an integrated downstream cascade that enables C. elegans to avoid high CO2. Here we show that cGMP regulation by GCY-9 and the PDE-1 phosphodiesterase controls BAG expression of a FMRFamide-related neuropeptide FLP-19 reporter (flp-19::GFP). This regulation is specific for CO2-sensing function of the BAG neurons, as loss of oxygen sensing function does not affect flp-19::GFP expression. We also found that expression of flp-19::GFP is controlled in parallel to GCY-9 by the activity-dependent transcription factor CREB (CRH-1) and the cAMP-dependent protein kinase (KIN-2) signaling pathway. We therefore show that two parallel pathways regulate neuropeptide gene expression in the BAG sensory neurons: the ability to sense changes in carbon dioxide and CREB transcription factor. Such regulation may be required in particular environmental conditions to enable sophisticated behavioral decisions to be performed.
authors.affiliation: Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria 3800, Australia.|Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen, Denmark.
authors.forename: Teresa
authors.initials: T
authors.lastname: Rojo Romanos
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen, Denmark.
authors.forename: Jakob Gramstrup
authors.initials: JG
authors.lastname: Petersen
authors.affiliation: Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria 3800, Australia.|Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen, Denmark.
authors.forename: Roger
authors.initials: R
authors.lastname: Pocock
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1 / Q000378:metabolism; D005786:Gene Expression Regulation; D009479:Neuropeptides / Q000096:biosynthesis*; D050705:Receptors, Guanylate Cyclase-Coupled / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D009479:Neuropeptides; D002245:Carbon Dioxide; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; C575916:GCY-9 protein, C elegans; D050705:Receptors, Guanylate Cyclase-Coupled; D006152:Cyclic GMP