DARPP-32 involvement in the photic pathway of the circadian system.
The multifunctional regulator of protein kinases and phosphatases dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) is an important molecular target of the dopamine signaling pathway. In the present study, we investigated the possible involvement of DARPP-32 regulation in the circadian system using DARPP-32 knock-out (KO) mice. These mice showed normal entrainment to a 12 h light/dark cycle and free run in constant darkness with a period similar to that of wild-type controls. After light exposure, however, the behavioral phase-delay response and the expression of light-induced clock gene mPer2 were attenuated in the DARPP-32 KO mice. Attenuated phase delays were also seen in animals bearing a point mutation in DARPP-32 at the PKA (Thr34) but not at the casein kinase I (Ser130) phosphorylation site. We next examined DARPP-32 expression in the retina and intergeniculate leaflet (IGL), both of which convey light information to the suprachiasmatic nucleus (SCN), the locus of a master circadian clock, and in the SCN itself. DARPP-32 was expressed in the retina but not in the IGL or the SCN. The results indicate that DARPP-32 is involved in the retinal pathway transmitting photic information that resets the circadian clock.
Yan
Lily
L
Department of Psychology, Columbia University, New York, New York 10027, USA.
Bobula
Jessica M
JM
Svenningsson
Per
P
Greengard
Paul
P
Silver
Rae
R
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001683:Biological Clocks / Q000502:physiology / Q000528:radiation effects; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000502:physiology* / Q000528:radiation effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000235:genetics / Q000378:metabolism*; D008027:Light; D055537:Light Signal Transduction / Q000502:physiology / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins; D010775:Photic Stimulation; D017354:Point Mutation / Q000235:genetics; D012160:Retina / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014795:Visual Pathways / Q000378:metabolism*
D018797:Cell Cycle Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009687:Nuclear Proteins; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; C497929:Ppp1r1b protein, mouse; D014157:Transcription Factors; D017868:Cyclic AMP-Dependent Protein Kinases