Cellular localization and function of DARPP-32 in the rodent retina.
The goal of the present study was to elucidate the role of DARPP-32 (dopamine- and cyclic adenosine 3'-5'-monophosphate-regulated phosphoprotein, 32 kDa) in retinal function. We examined mouse and rat retinas for the presence of DARPP-32 by immunocytochemistry. In both rodent retinas DARPP-32 immunoreactivity was localized to horizontal and AII amacrine neurons and to the Mueller glial cells, using immuno-double labelling. Additional unidentified neurons in the amacrine cell layer also showed DARPP-32 immunoreactivity. Using mice entrained to a 12-12 h light-dark cycle, we found that exposure to light presented during the dark phase significantly enhanced phosphorylation of DARPP-32 at threonine (Thr) 34 and phosphorylation of the ionotropic glutamate receptor subunit GluR1 at serine (Ser) 845, as measured by immunoblots. However, light also increased Ser 845-GluR1 phosphorylation in DARPP-32-knockout mice. When a dopamine D1 receptor antagonist was injected into the eye prior to light exposure, phosphorylation of both Thr 34-DARPP-32 and Ser 845-GluR1 was significantly reduced. These data indicate that DARPP-32 participates in dopamine-mediated modifications of retinal function. We also tested for a possible circadian rhythm of Thr 34- and Thr 75-DARPP-32 and Ser 845-GluR1 expression. No significant circadian rhythm of either DARPP-32 or GluR1 phosphorylation was found.
Witkovsky
Paul
P
Department of Ophthalmology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. pw20@nyu.edu
Svenningsson
Per
P
Yan
Lily
L
Bateup
Helen
H
Silver
Rae
R
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002940:Circadian Rhythm / Q000235:genetics; D018492:Dopamine Antagonists / Q000494:pharmacology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000172:deficiency / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000378:metabolism*; D012377:Rodentia; D012694:Serine; D013912:Threonine
D001552:Benzazepines; D018492:Dopamine Antagonists; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D012694:Serine; D013912:Threonine