Localization of ARPP-90, a major 90 kiloDalton basal ganglion-enriched substrate for cyclic AMP-dependent protein kinase, in striatonigral neurons in the rat brain

Abstract

Cyclic AMP-regulated phosphoproteins with specific cellular localizations in brain represent important targets through which this second messenger system can mediate or modulate distinct neurotransmitter signals. This study reports that two cyclic AMP-regulated phosphoproteins ( M r 90,000 and 93,000) found in brain share several properties, including similar isoelectric points and similar phosphopeptide maps. This protein doublet is particularly enriched in the forebrain basal ganglia, but it can also be found in the substantia nigra, a brainstem region which is a major target for fibers from the forebrain basal ganglia. Quinolic acid lesions of neurons in the neostriatum decrease the levels of the 90 93 kDa phosphoprotein doublet to about the same extent as they reduce the levels of DARPP-32, a phosphoprotein specifically enriched in striatonigral medium-sized spiny neurons. These reductions are seen in both the neostriatum and the substantia nigra. Therefore, within the basal ganglia, the 90 93 kDa phosphoprotein doublet, termed adenosine 3′:5′-monophosphate-regulated phosphoprotein, M r = 90,000 (ARPP-90), is largely, if not solely, present in striatonigral cells and fibers. The specific localization in these neurons suggests that ARPP-90 could be important in receptor-regulated, cyclic AMP-mediated functions in the striatonigral neurons.