title: PKC-2 phosphorylation of UNC-18 Ser322 in AFD neurons regulates temperature dependency of locomotion.
abstract: Diacylglycerol (DAG)/protein kinase C (PKC) signaling plays an integral role in the regulation of neuronal function. This is certainly true in Caenorhabditis elegans and in particular for thermosensory signaling and behavior. Downstream molecular targets for transduction of this signaling cascade remain, however, virtually uncharacterized. We investigated whether PKC phosphorylation of Munc18-1, an essential protein in vesicle trafficking and exocytosis, was the downstream effector for DAG regulation of thermosensory behavior. We demonstrate here that the C. elegans ortholog of Munc18-1, UNC-18, was phosphorylated in vitro at Ser322. Transgenic rescue of unc-18-null worms with Ser322 phosphomutants displayed altered thermosensitivity. C. elegans expresses three DAG-regulated PKCs, and blocking UNC-18 Ser322 phosphorylation was phenocopied only by deletion of calcium-activated PKC-2. Expression of nonphosphorylatable UNC-18 S322A, either pan-neuronally or specifically in AFD thermosensory neurons, converted wild-type worms to a pkc-2-null phenotype. These data demonstrate that an individual DAG-dependent thermosensory behavior of an organism is effected specifically by the downstream PKC-2 phosphorylation of UNC-18 on Ser322 in AFD neurons.
authors.affiliation: Department of Cellular and Molecular Physiology, The Physiological Laboratory, University of Liverpool, Liverpool L69 3BX, United Kingdom.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Edwards
authors.forename: James R
authors.initials: JR
authors.lastname: Johnson
authors.forename: Kimberley
authors.initials: K
authors.lastname: Rankin
authors.forename: Rosalind E
authors.initials: RE
authors.lastname: Jenkins
authors.forename: Carl
authors.initials: C
authors.lastname: Maguire
authors.forename: Alan
authors.initials: A
authors.lastname: Morgan
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burgoyne
authors.forename: Jeff W
authors.initials: JW
authors.lastname: Barclay
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004075:Diglycerides / Q000378:metabolism / Q000502:physiology; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology; D008124:Locomotion / Q000502:physiology*; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050765:Qa-SNARE Proteins / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013697:Thermosensing / Q000502:physiology*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C011439:1,2-diacylglycerol; D029742:Caenorhabditis elegans Proteins; D004075:Diglycerides; D007527:Isoenzymes; D010750:Phosphoproteins; D050765:Qa-SNARE Proteins; C082636:Unc-18 protein, C elegans; D033921:Vesicular Transport Proteins; D011493:Protein Kinase C