Regulation of stargazin synaptic trafficking by C-terminal PDZ ligand phosphorylation in bidirectional synaptic plasticity

Emma L.A. Stein, Dane M. Chetkovich

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Stargazin is a transmembrane α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) receptor regulatory protein that controls the surface and synaptic expression of AMPA-type glutamate receptors (AMPARs). Synaptic anchoring of AMPARs is influenced by the interaction between stargazin's C-terminal post-synaptic density-95 (PSD-95)/discs large/zona occludens-1 (PDZ) ligand and the synaptic scaffolding protein PSD-95. Phosphorylation of the stargazin PDZ ligand by protein kinase A (PKA) disrupts stargazin's interaction with PSD-95, but whether this phosphorylation plays a role in activity-dependent regulation of stargazin/AMPAR synaptic trafficking is unknown. Here, we show that stargazin is phosphorylated within the PDZ ligand at threonine residue 321 (T321) by mitogen-activated protein kinases (MAPKs) as well as PKA. By expressing constructs that selectively block T321 phosphorylation by either PKA or MAPKs, we show that stargazin T321 phosphorylation is required for activity-dependent changes in stargazin synaptic clustering in dissociated rat hippocampal neuron cultures. Specifically, we find that mutations that block stargazin T321 phosphorylation by PKA prevent activity-dependent increases in stargazin synaptic clustering, whereas a point mutant that blocks MAPK phosphorylation of T321 prevents activity-dependent decreases in stargazin synaptic clustering. Taken together, our studies implicate phosphorylation of stargazin T321 by PKA and MAPKs in bidirectional control of stargazin/AMPAR synaptic clustering during synaptic plasticity.

Original languageEnglish (US)
Pages (from-to)42-53
Number of pages12
JournalJournal of neurochemistry
Volume113
Issue number1
DOIs
StatePublished - Apr 2010

Keywords

  • AMPA receptor trafficking
  • Cultured neurons
  • Long-term depression
  • Long-term potentiation
  • PDZ ligand phosphorylation
  • Stargazin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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