EntrezGeneSummary | Midbraindopaminergicneuronsplayacriticalroleinmultiplebrainfunctions,andabnormalsignalingthroughdopaminergicpathwayshasbeenimplicatedinseveralmajorneurologicandpsychiatricdisorders.Onewell-studiedtargetfortheactionsofdopamineisDARPP32.Inthedenselydopamine-andglutamate-innervatedratcaudate-putamen,DARPP32isexpressedinmedium-sizedspinyneurons(OuimetandGreengard,1990[PubMed2191086])thatalsoexpressdopamineD1receptors(WalaasandGreengard,1984[PubMed6319627]).ThefunctionofDARPP32seemstoberegulatedbyreceptorstimulation.Bothdopaminergicandglutamatergic(NMDA)receptorstimulationregulatetheextentofDARPP32phosphorylation,butinoppositedirections(Halpainetal.,1990[PubMed2153935]).DopamineD1receptorstimulationenhancescAMPformation,resultinginthephosphorylationofDARPP32(WalaasandGreengard,1984[PubMed6319627]);phosphorylatedDARPP32isapotentproteinphosphatase-1(seeMIM176875)inhibitor(Hemmingsetal.,1984[PubMed6087160]).NMDAreceptorstimulationelevatesintracellularcalcium,whichleadstoactivationofcalcineurinanddephosphorylationofphospho-DARPP32,therebyreducingthephosphatase-1inhibitoryactivityofDARPP32(Halpainetal.,1990[PubMed2153935]).[suppliedbyOMIM] |