PT  - JOURNAL ARTICLE
AU  - Yudong Yao
AU  - Matthew Taylor Kelly
AU  - Sreedharan Sajikumar
AU  - Peter Serrano
AU  - Dezhi Tian
AU  - Peter John Bergold
AU  - Julietta Uta Frey
AU  - Todd Charlton Sacktor
TI  - PKMζ Maintains Late Long-Term Potentiation by <em>N</em>-Ethylmaleimide-Sensitive Factor/GluR2-Dependent Trafficking of Postsynaptic AMPA Receptors
AID  - 10.1523/JNEUROSCI.0223-08.2008
DP  - 2008 Jul 30
TA  - The Journal of Neuroscience
PG  - 7820--7827
VI  - 28
IP  - 31
4099  - http://www.jneurosci.org/content/28/31/7820.short
4100  - http://www.jneurosci.org/content/28/31/7820.full
SO  - J. Neurosci.2008 Jul 30; 28
AB  - 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 Mζ (PKMζ), is a core molecule maintaining late-LTP. Here we show that PKMζ 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 PKMζ 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. PKMζ 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 PKMζ-mediated AMPAR potentiation. During LTP maintenance, PKMζ 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, PKMζ maintains late-LTP by persistently modifying NSF/GluR2-dependent AMPAR trafficking to favor receptor insertion into postsynaptic sites.