Calcium and SOL Protease Mediate Temperature Resetting of Circadian Clocks

Cell. 2015 Nov 19;163(5):1214-1224. doi: 10.1016/j.cell.2015.10.031.

Abstract

Circadian clocks integrate light and temperature input to remain synchronized with the day/night cycle. Although light input to the clock is well studied, the molecular mechanisms by which circadian clocks respond to temperature remain poorly understood. We found that temperature phase shifts Drosophila circadian clocks through degradation of the pacemaker protein TIM. This degradation is mechanistically distinct from photic CRY-dependent TIM degradation. Thermal TIM degradation is triggered by cytosolic calcium increase and CALMODULIN binding to TIM and is mediated by the atypical calpain protease SOL. This thermal input pathway and CRY-dependent light input thus converge on TIM, providing a molecular mechanism for the integration of circadian light and temperature inputs. Mammals use body temperature cycles to keep peripheral clocks synchronized with their brain pacemaker. Interestingly, downregulating the mammalian SOL homolog SOLH blocks thermal mPER2 degradation and phase shifts. Thus, we propose that circadian thermosensation in insects and mammals share common principles.

Publication types

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

MeSH terms

  • Animals
  • Biological Clocks
  • Calcium Signaling
  • Calmodulin / metabolism
  • Calpain
  • Circadian Clocks*
  • Circadian Rhythm
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / physiology*
  • Male
  • Mammals / physiology
  • Nerve Tissue Proteins / metabolism*
  • Proteolysis

Substances

  • Calmodulin
  • Drosophila Proteins
  • Nerve Tissue Proteins
  • tim protein, Drosophila
  • Calpain
  • sol protein, Drosophila