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.
Yan
Z
Z
Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, New York 10021, USA.
Hsieh-Wilson
L
L
Feng
J
J
Tomizawa
K
K
Allen
P B
PB
Fienberg
A A
AA
Nairn
A C
AC
Greengard
P
P
D000818:Animals; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism* / Q000502:physiology; D008840:Microfilament Proteins / Q000378:metabolism*; D017072:Neostriatum / Q000166:cytology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins; D054645:Protein Phosphatase 1; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism* / Q000502:physiology; D000099273:Neurabins
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004791:Enzyme Inhibitors; D007473:Ion Channels; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D010749:Phosphoprotein Phosphatases; D010750:Phosphoproteins; D054645:Protein Phosphatase 1; D018091:Receptors, AMPA; D000099273:Neurabins