A putative substrate of Protein Kinase G for the photic transduction pathway of the circadian clock

ALESSANDRO MARIA SOLEDAD; PLANO SANTIAGO ANDRÉS; ENDO SHOGO; GOLOMBEK DIEGO ANDRÉS.; JUAN JOSE CHIESA

Simposio; XIII Latin American Symposium on Chronobiology (LASC); 2015

Circadian clocks drive rhythms in physiology and behavior, providing a selective advantage by enabling organisms to synchronize to 24h environmental day using light-dark transitions as the main phase-shifting signal. In mammals, light input from the retina reaches the master circadian clock in the hypothalamic suprachiasmatic nucleus (SCN) through glutamatergic afferents. Both the phase-shift induced, and the pathway activated, depends on the zeitgeber time (ZT) at which light is applied (ZT12 is defined at locomotor activity onset). Light pulse (LP) at ZT18 causes phase-advances by activation of the nitric oxide-guanylate cyclase-protein kinase G (NO-GC- PKG) pathway, leading to enhanced circadian gene transcription by still unknown components. Previous studies show that PKG interacts with G substrate (GS), which has been identified in SCN and cerebellum. We found that both GS and its phosphorylated form (p-GS) have a restricted distribution at the hamster SCN, having GS levels a daily rhythm peaking at ZT18. Increased SCN levels of p-GS were found after a LP delivered to hamsters at the same ZT. In addition, treatment with KT-5823, a specific inhibitor of PKG, decreased this photic induction of p-GS levels, while sildenafil, a strong activator of PKG, increased p-GS photic levels. These results provide evidence that photic NO-GC-PKG pathway involves downstream phosphorylation of GS by PKG to synchronize the SCN clock.