title: PKA-GluA1 coupling via AKAP5 controls AMPA receptor phosphorylation and cell-surface targeting during bidirectional homeostatic plasticity.
abstract: Bidirectional synaptic plasticity occurs locally at individual synapses during long-term potentiation (LTP) or long-term depression (LTD), or globally during homeostatic scaling. LTP, LTD, and homeostatic scaling alter synaptic strength through changes in postsynaptic AMPA-type glutamate receptors (AMPARs), suggesting the existence of overlapping molecular mechanisms. Phosphorylation controls AMPAR trafficking during LTP/LTD. We addressed the role of AMPAR phosphorylation during homeostatic scaling. We observed bidirectional changes of the levels of phosphorylated GluA1 S845 during scaling, resulting from a loss of protein kinase A (PKA) from synapses during scaling down and enhanced activity of PKA in synapses during scaling up. Increased phosphorylation of S845 drove scaling up, while a knockin mutation of S845, or knockdown of the scaffold AKAP5, blocked scaling up. Finally, we show that AMPARs scale differentially based on their phosphorylation status at S845. These results show that rearrangement in PKA signaling controls AMPAR phosphorylation and surface targeting during homeostatic plasticity.
authors.affiliation: Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Hunterian 1001, 725 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Graham H
authors.initials: GH
authors.lastname: Diering
authors.affiliation: Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Hunterian 1001, 725 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Ahleah S
authors.initials: AS
authors.lastname: Gustina
authors.affiliation: Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Hunterian 1001, 725 North Wolfe Street, Baltimore, MD 21205, USA. Electronic address: rhuganir@jhmi.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
mesh_terms: D054758:A Kinase Anchor Proteins / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000502:physiology
chemical_list: D054758:A Kinase Anchor Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D018091:Receptors, AMPA; C415703:Akap5 protein, rat