Caenorhabditis elegans TRPV ion channel regulates 5HT biosynthesis in chemosensory neurons.
Serotonin (5HT) is a pivotal signaling molecule that modulates behavioral and endocrine responses to diverse chemical and physical stimuli. We report cell-specific regulation of 5HT biosynthesis by transient receptor potential V (TRPV) ion channels in C. elegans. Mutations in the TRPV genes osm-9 or ocr-2 dramatically downregulate the expression of the gene encoding the 5HT synthesis enzyme tryptophan hydroxylase (tph-1) in the serotonergic chemosensory neurons ADF, but neither the mutation nor the double mutation of both channel genes affects other types of serotonergic neurons. The TRPV genes are expressed in the ADF neurons but not in other serotonergic neurons, and act cell-autonomously to regulate a neuron-specific transcription program. Whereas in olfactory neurons OSM-9 and OCR-2 function is dependent on ODR-3 Galpha, the activity of ODR-3 or two other Galpha proteins expressed in the ADF neurons is not required for upregulating tph-1 expression, thus the TRPV ion channels in different neurons may be regulated by different mechanisms. A gain-of-function mutation in CaMKII UNC-43 partially suppresses the downregulation of tph-1 in the TRPV mutants, thus CaMKII may be an effector of the TRPV signaling. Mutations in the TRPV genes cause worms developmentally arrest at the Dauer stage. This developmental defect is due in part to reduced 5HT inputs into daf-2/insulin neuroendocrine signaling.
Department of Anatomy and Neurobiology, College of Medicine, University of California Irvine, Irvine, CA 92697-4040, USA.
Shenyuan
S
Zhang
Irina
I
Sokolchik
Gabriela
G
Blanco
Ji Ying
JY
Sze
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002628:Chemoreceptor Cells / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000096:biosynthesis*; D015398:Signal Transduction / Q000502:physiology; D050916:TRPV Cation Channels; D050051:Transient Receptor Potential Channels; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D007473:Ion Channels; D009419:Nerve Tissue Proteins; C464590:OCR-2 protein, C elegans; C108820:OSM-9 protein, C elegans; D011993:Recombinant Fusion Proteins; D050916:TRPV Cation Channels; D050051:Transient Receptor Potential Channels; D012701:Serotonin; D014365:Tryptophan Hydroxylase; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517679:unc-43 protein, C elegans