A Calcium- and Diacylglycerol-Stimulated Protein Kinase C (PKC), Caenorhabditis elegans PKC-2, Links Thermal Signals to Learned Behavior by Acting in Sensory Neurons and Intestinal Cells

Ca2+ - and diacylglycerol (DAG)-activated protein kinase C (cPKC) promotes learning and behavioral plasticity. However, knowledge ofin vivo regulation and exact functions of cPKCs that affect behavior is limited. We show that PKC-2, aCaenorhabditis elegans cPKC, is essential for a complex behavior, thermotaxis.C. elegans memorizes a nutrient-associated cultivation temperature (Tc ) and migrates along theTc within a 17 to 25°C gradient.pkc-2 gene disruption abrogated thermotaxis; a PKC-2 transgene, driven by endogenouspkc-2 promoters, restored thermotaxis behavior inpkc-2 −/− animals. Cell-specific manipulation of PKC-2 activity revealed that thermotaxis is controlled by cooperative PKC-2-mediated signaling in both AFD sensory neurons and intestinal cells. Cold-directed migration (cryophilic drive) precedesTc tracking during thermotaxis. Analysis of temperature-directed behaviors elicited by persistent PKC-2 activation or inhibition in AFD (or intestine) disclosed that PKC-2 regulates initiation and duration of cryophilic drive. In AFD neurons, PKC-2 is a Ca2+ sensor and signal amplifier that operates downstream from cyclic GMP-gated cation channels and distal guanylate cyclases. UNC-18, which regulates neurotransmitter and neuropeptide release from synaptic vesicles, is a critical PKC-2 effector in AFD. UNC-18 variants, created by mutating Ser311 or Ser322 , disrupt thermotaxis and suppress PKC-2-dependent cryophilic migration.