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TARP phosphorylation regulates synaptic AMPA receptors through lipid bilayers.

Neurons use neurotransmitters to communicate across synapses, constructing neural circuits in the brain. AMPA-type glutamate receptors are the predominant excitatory neurotransmitter receptors mediating fast synaptic transmission. AMPA receptors localize at synapses by forming protein complexes with transmembrane AMPA receptor regulatory proteins (TARPs) and PSD-95-like membrane-associated guanylate kinases. Among the three classes of ionotropic glutamate receptors (AMPA, NMDA, and kainate type), AMPA receptor activity is most regulatable by neuronal activity to adjust synaptic strength. Here, we mutated the prototypical TARP, stargazin, and found that TARP phosphorylation regulates synaptic AMPA receptor activity in vivo. We also found that stargazin interacts with negatively charged lipid bilayers in a phosphorylation-dependent manner and that the lipid interaction inhibited stargazin binding to PSD-95. Cationic lipids dissociated stargazin from lipid bilayers and enhanced synaptic AMPA receptor activity in a stargazin phosphorylation-dependent manner. Thus, TARP phosphorylation plays a critical role in regulating AMPA receptor-mediated synaptic transmission via a lipid bilayer interaction.

Pubmed ID: 20547132

Authors

  • Sumioka A
  • Yan D
  • Tomita S

Journal

Neuron

Publication Data

June 10, 2010

Associated Grants

  • Agency: NIMH NIH HHS, Id: MH077939
  • Agency: NIDA NIH HHS, Id: P30 DA018343
  • Agency: NIDA NIH HHS, Id: P30DA018343
  • Agency: NIMH NIH HHS, Id: R01 MH077939
  • Agency: NIMH NIH HHS, Id: R01 MH077939-01A2
  • Agency: NIMH NIH HHS, Id: R01 MH077939-02

Mesh Terms

  • Animals
  • CHO Cells
  • Calcium Channels
  • Cricetinae
  • Cricetulus
  • Gene Knock-In Techniques
  • Lipid Bilayers
  • Membrane Proteins
  • Mice
  • Mice, Mutant Strains
  • Phosphorylation
  • Receptors, AMPA
  • Synapses