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Regulation of Synaptic Transmission and Plasticity by Protein Phosphatase 1

Karl Foley, Cody McKee, Angus C. Nairn and Houhui Xia
Journal of Neuroscience 7 April 2021, 41 (14) 3040-3050; DOI: https://doi.org/10.1523/JNEUROSCI.2026-20.2021
Karl Foley
1Neuroscience Graduate Program, Department of Neuroscience, University of Rochester Medical Center, Rochester, New York 14642
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Cody McKee
1Neuroscience Graduate Program, Department of Neuroscience, University of Rochester Medical Center, Rochester, New York 14642
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Angus C. Nairn
2Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06511
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Houhui Xia
3Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York 14642
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Abstract

Protein phosphatases, by counteracting protein kinases, regulate the reversible phosphorylation of many substrates involved in synaptic plasticity, a cellular model for learning and memory. A prominent phosphatase regulating synaptic plasticity and neurologic disorders is the serine/threonine protein phosphatase 1 (PP1). PP1 has three isoforms (α, β, and γ, encoded by three different genes), which are regulated by a vast number of interacting subunits that define their enzymatic substrate specificity. In this review, we discuss evidence showing that PP1 regulates synaptic transmission and plasticity, as well as presenting novel models of PP1 regulation suggested by recent experimental evidence. We also outline the required targeting of PP1 by neurabin and spinophilin to achieve substrate specificity at the synapse to regulate AMPAR and NMDAR function. We then highlight the role of inhibitor-2 in regulating PP1 function in plasticity, including its positive regulation of PP1 function in vivo in memory formation. We also discuss the distinct function of the three PP1 isoforms in synaptic plasticity and brain function, as well as briefly discuss the role of inhibitory phosphorylation of PP1, which has received recent emphasis in the regulation of PP1 activity in neurons.

  • protein phosphatase 1
  • inhibitor-2
  • synaptic transmission
  • neurabin
  • LTP
  • LTD

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The Journal of Neuroscience: 41 (14)
Journal of Neuroscience
Vol. 41, Issue 14
7 Apr 2021
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Regulation of Synaptic Transmission and Plasticity by Protein Phosphatase 1
Karl Foley, Cody McKee, Angus C. Nairn, Houhui Xia
Journal of Neuroscience 7 April 2021, 41 (14) 3040-3050; DOI: 10.1523/JNEUROSCI.2026-20.2021

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Regulation of Synaptic Transmission and Plasticity by Protein Phosphatase 1
Karl Foley, Cody McKee, Angus C. Nairn, Houhui Xia
Journal of Neuroscience 7 April 2021, 41 (14) 3040-3050; DOI: 10.1523/JNEUROSCI.2026-20.2021
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Keywords

  • protein phosphatase 1
  • inhibitor-2
  • synaptic transmission
  • neurabin
  • LTP
  • LTD

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