title: PKM zeta maintains late long-term potentiation by N-ethylmaleimide-sensitive factor/GluR2-dependent trafficking of postsynaptic AMPA receptors.
abstract: Although the maintenance mechanism of late long-term potentiation (LTP) is critical for the storage of long-term memory, the expression mechanism of synaptic enhancement during late-LTP is unknown. The autonomously active protein kinase C isoform, protein kinase Mzeta (PKMzeta), is a core molecule maintaining late-LTP. Here we show that PKMzeta maintains late-LTP through persistent N-ethylmaleimide-sensitive factor (NSF)/glutamate receptor subunit 2 (GluR2)-dependent trafficking of AMPA receptors (AMPARs) to the synapse. Intracellular perfusion of PKMzeta into CA1 pyramidal cells causes potentiation of postsynaptic AMPAR responses; this synaptic enhancement is mediated through NSF/GluR2 interactions but not vesicle-associated membrane protein-dependent exocytosis. PKMzeta may act through NSF to release GluR2-containing receptors from a reserve pool held at extrasynaptic sites by protein interacting with C-kinase 1 (PICK1), because disrupting GluR2/PICK1 interactions mimic and occlude PKMzeta-mediated AMPAR potentiation. During LTP maintenance, PKMzeta directs AMPAR trafficking, as measured by NSF/GluR2-dependent increases of GluR2/3-containing receptors in synaptosomal fractions from tetanized slices. Blocking this trafficking mechanism reverses established late-LTP and persistent potentiation at synapses that have undergone synaptic tagging and capture. Thus, PKMzeta maintains late-LTP by persistently modifying NSF/GluR2-dependent AMPAR trafficking to favor receptor insertion into postsynaptic sites.
authors.affiliation: The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology, State University of New York, Downstate Medical Center, Brooklyn, New York 11203, USA.
authors.forename: Yudong
authors.initials: Y
authors.lastname: Yao
authors.forename: Matthew Taylor
authors.initials: MT
authors.lastname: Kelly
authors.forename: Sreedharan
authors.initials: S
authors.lastname: Sajikumar
authors.forename: Peter
authors.initials: P
authors.lastname: Serrano
authors.forename: Dezhi
authors.initials: D
authors.lastname: Tian
authors.forename: Peter John
authors.initials: PJ
authors.lastname: Bergold
authors.forename: Julietta Uta
authors.initials: JU
authors.lastname: Frey
authors.forename: Todd Charlton
authors.initials: TC
authors.lastname: Sacktor
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D007527:Isoenzymes / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism / Q000502:physiology*
chemical_list: D007527:Isoenzymes; D018091:Receptors, AMPA; D011493:Protein Kinase C; C504730:protein kinase M zeta, rat; D052066:N-Ethylmaleimide-Sensitive Proteins; C104722:glutamate receptor ionotropic, AMPA 2