Regulation of GluA1 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor function by protein kinase C at serine-818 and threonine-840

Meagan A. Jenkins, Gordon Wells, Julia Bachman, James P. Snyder, Andrew Jenkins, Richard L Huganir, Robert E. Oswald, Stephen F. Traynelis

Research output: Contribution to journalArticle

Abstract

Three residues within the AMPA (α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid) receptor subunit GluA1 C terminus (Ser818, Ser831, Thr840) can be phosphorylated by Ca2+/phospholipiddependent protein kinase (PKC). Here, we show that PKC phosphorylation of GluA1 Ser818 or Thr840 enhances the weighted mean channel conductance without altering the response time course or agonist potency. These data support the idea that these residues constitute a hyper-regulatory domain for the AMPA receptor. Introduction of phosphomimetic mutations increases conductance only at these three sites within the proximal C terminus, consistent with a structural model with a flexible linker connecting the distal C-terminal domain to the more proximal domain containing a helix bracketed by Ser831 and Thr840. NMR spectra support this model and raise the possibility that phosphorylation can alter the configuration of this domain. Our findings provide insight into the structure and function of the C-terminal domain of GluA1, which controls AMPA receptor function and trafficking during synaptic plasticity in the central nervous system.

Original languageEnglish (US)
Pages (from-to)618-629
Number of pages12
JournalMolecular Pharmacology
Volume85
Issue number4
DOIs
StatePublished - Apr 2014

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AMPA Receptors
Threonine
Serine
Phosphorylation
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Neuronal Plasticity
Acids
Structural Models
Protein Kinases
Reaction Time
Central Nervous System
Mutation
receptors for activated C kinase

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Regulation of GluA1 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor function by protein kinase C at serine-818 and threonine-840. / Jenkins, Meagan A.; Wells, Gordon; Bachman, Julia; Snyder, James P.; Jenkins, Andrew; Huganir, Richard L; Oswald, Robert E.; Traynelis, Stephen F.

In: Molecular Pharmacology, Vol. 85, No. 4, 04.2014, p. 618-629.

Research output: Contribution to journalArticle

Jenkins, Meagan A. ; Wells, Gordon ; Bachman, Julia ; Snyder, James P. ; Jenkins, Andrew ; Huganir, Richard L ; Oswald, Robert E. ; Traynelis, Stephen F. / Regulation of GluA1 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor function by protein kinase C at serine-818 and threonine-840. In: Molecular Pharmacology. 2014 ; Vol. 85, No. 4. pp. 618-629.
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