Circadian regulation of intracellular G-protein signalling mediates intercellular synchrony and rhythmicity in the suprachiasmatic nucleus

Nat Commun. 2011:2:327. doi: 10.1038/ncomms1316.


Synchronous oscillations of thousands of cellular clocks in the suprachiasmatic nucleus (SCN), the circadian centre, are coordinated by precisely timed cell-cell communication, the principle of which is largely unknown. Here we show that the amount of RGS16 (regulator of G protein signalling 16), a protein known to inactivate Gαi, increases at a selective circadian time to allow time-dependent activation of intracellular cyclic AMP signalling in the SCN. Gene ablation of Rgs16 leads to the loss of circadian production of cAMP and as a result lengthens circadian period of behavioural rhythm. The temporally precise regulation of the cAMP signal by clock-controlled RGS16 is needed for the dorsomedial SCN to maintain a normal phase-relationship to the ventrolateral SCN. Thus, RGS16-dependent temporal regulation of intracellular G protein signalling coordinates the intercellular synchrony of SCN pacemaker neurons and thereby defines the 24 h rhythm in behaviour.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Circadian Rhythm*
  • Cyclic AMP / metabolism
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Period Circadian Proteins / genetics
  • Period Circadian Proteins / metabolism
  • Periodicity
  • RGS Proteins / genetics
  • RGS Proteins / metabolism*
  • Signal Transduction
  • Suprachiasmatic Nucleus / physiology*


  • Per1 protein, mouse
  • Period Circadian Proteins
  • RGS Proteins
  • RGS16 protein
  • Cyclic AMP

Associated data

  • GEO/GSE28574