Faculty Collaboration Database

Plk2 attachment to NSF induces homeostatic removal of GluA2 during chronic overexcitation. Nat Neurosci 2010 Oct;13(10):1199-207

Date

08/31/2010

Pubmed ID

20802490

Pubmed Central ID

PMC2947592

DOI

10.1038/nn.2624

Scopus ID

2-s2.0-77957279696 (requires institutional sign-in at Scopus site)   59 Citations

Abstract

Trafficking of AMPA receptors (AMPARs) is important for many forms of synaptic plasticity. However, the link between activity and resulting synaptic alterations is not fully understood. We identified a direct interaction between N-ethylmaleimide-sensitive fusion protein (NSF), an ATPase involved in membrane fusion events and stabilization of surface AMPARs, and Polo-like kinase- 2 (Plk2), an activity-inducible kinase that homeostatically decreases excitatory synapse number and strength. Plk2 disrupted the interaction of NSF with the GluA2 subunit of AMPARs, promoting extensive loss of surface GluA2 in rat hippocampal neurons, greater association of GluA2 with adaptor proteins PICK1 and GRIP1, and decreased synaptic AMPAR current. Plk2 engagement of NSF, but not Plk2 kinase activity, was required for this mechanism and occurred through a motif in the Plk2 protein that was independent of the canonical polo box interaction sites. These data reveal that heightened synaptic activity, acting through Plk2, leads to homeostatic decreases in surface AMPAR expression via the direct dissociation of NSF from GluA2.

Author List

Evers DM, Matta JA, Hoe HS, Zarkowsky D, Lee SH, Isaac JT, Pak DT

Author

Sang H. Lee PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Amino Acid Motifs
Animals
Carrier Proteins
Cells, Cultured
Cytoskeletal Proteins
Embryo, Mammalian
Endocytosis
GABA Antagonists
Gene Expression Regulation
Green Fluorescent Proteins
Hippocampus
Homeostasis
Humans
Immunoprecipitation
Intracellular Signaling Peptides and Proteins
Microscopy, Confocal
N-Ethylmaleimide-Sensitive Proteins
Nerve Tissue Proteins
Neurons
Nuclear Proteins
Picrotoxin
Protein Binding
Protein Transport
RNA Interference
Rats
Receptors, AMPA
Synapses
Time Factors
Transfection