Protein phosphatase 1 modulation of neostriatal AMPA channels: regulation by DARPP–32 and spinophilin

Modulation of AMPA−type glutamate channels is important for synaptic plasticity. Here we provide physiological evidence that the activity of AMPA channels is regulated by protein phosphatase 1 (PP−1) in neostriatal neurons and identify two distinct molecular mechanisms of this regulation. One mechanism involves control of PP−1 catalytic activity by DARPP−32, a dopamine− and cAMP−regulated phosphoprotein highly enriched in neostriatum. The other involves binding of PP−1 to spinophilin, a protein that colocalizes PP−1 with AMPA receptors in postsynaptic densities. The results suggest that regulation of anchored PP−1 is important for AMPA−receptor−mediated synaptic transmission and plasticity.