The balance between cytoplasmic and nuclear CaM kinase-1 signaling controls the operating range of noxious heat avoidance

Neuron. 2014 Dec 3;84(5):983-96. doi: 10.1016/j.neuron.2014.10.039. Epub 2014 Nov 20.


Through encounters with predators, competitors, and noxious stimuli, animals have evolved defensive responses that minimize injury and are essential for survival. Physiological adaptation modulates the stimulus intensities that trigger such nocifensive behaviors, but the molecular networks that define their operating range are largely unknown. Here, we identify a gain-of-function allele of the cmk-1 CaMKI gene in C. elegans and show that loss of the regulatory domain of the CaMKI enzyme produces thermal analgesia and shifts the operating range for nocifensive heat avoidance to higher temperatures. Such analgesia depends on nuclear CMK-1 signaling, while cytoplasmic CMK-1 signaling lowers the threshold for thermal avoidance. CMK-1 acts downstream of heat detection in thermal receptor neurons and controls neuropeptide release. Our results establish CaMKI as a key regulator of the operating range for nocifensive behaviors and suggest strategies for producing thermal analgesia through the regulation of CaMKI-dependent signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Animals, Genetically Modified
  • Avoidance Learning / physiology
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Type 1 / genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Type 1 / metabolism*
  • Cell Nucleolus / metabolism
  • Cytoplasm / metabolism
  • Escape Reaction / physiology*
  • Hot Temperature / adverse effects*
  • Mutagenesis
  • Mutation / genetics
  • Neurons / cytology*
  • Neuropeptides / metabolism
  • Nociception / physiology*
  • Sensory Receptor Cells
  • Signal Transduction / genetics
  • Signal Transduction / physiology*


  • Caenorhabditis elegans Proteins
  • Neuropeptides
  • Calcium-Calmodulin-Dependent Protein Kinase Type 1