Distribution of protein phosphatases-1 alpha and -1 gamma 1 and the D(1) dopamine receptor in primate prefrontal cortex: Evidence for discrete populations of spines.
The function of G protein-coupled receptors depends on the availability of the appropriate signal transduction proteins in close proximity to the receptor. We have examined and quantified in primate prefrontal cortex the subcellular distribution of two isoforms of protein phosphatase-1 (PP1), PP1 alpha and PP1 gamma 1, which are components of the signal transduction pathway accessed by the D(1) dopamine receptor. Both PP1 alpha- and PP1 gamma 1-labeled puncta are seen in cortex, basal ganglia, hippocampus, and thalamus. Viewed with the electron microscope, both PP1 isoforms are selectively localized to dendritic spines and are found in different percentages of spines; PP1 alpha is present in roughly 70% and PP1 gamma 1 in roughly 40% of dendritic spines. Our analysis indicates that three populations of spines are defined by the distribution of these PP1 isoforms: those that contain both PP1 alpha and PP1 gamma 1, those that contain only PP1 alpha and those that contain neither. The D(1) receptor is present in a subset of the population that contains both PP1 alpha and PP1 gamma 1. The nonhomogeneous distribution of signal transduction proteins in the spines and dendrites of cortical pyramidal cells may help to explain differences in the actions of receptors that nominally use the same signal-transduction pathway.
Muly
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Department of Psychiatry and Behavioral Science, Division of Neuroscience, Yerkes Primate Research Center, Center for Behavioral Neuroscience, Emory University, Atlanta, Georgia 30329, USA. emuly@emory.edu
Greengard
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Goldman-Rakic
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PS
D000818:Animals; D003712:Dendrites / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008251:Macaca / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism*; D054645:Protein Phosphatase 1; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D014018:Tissue Distribution
D007527:Isoenzymes; D017448:Receptors, Dopamine D2; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1