Clathrin adaptor AP2 and NSF interact with overlapping sites of GluR2 and play distinct roles in AMPA receptor trafficking and hippocampal LTD. Neuron 2002 Nov 14;36(4):661-74
Date
11/21/2002Pubmed ID
12441055DOI
10.1016/s0896-6273(02)01024-3Scopus ID
2-s2.0-0037079062 (requires institutional sign-in at Scopus site) 373 CitationsAbstract
Proteins that bind to the cytoplasmic tails of AMPA receptors control receptor trafficking and thus the strength of postsynaptic responses. Here we show that AP2, a clathrin adaptor complex important for endocytosis, associates with a region of GluR2 that overlaps the NSF binding site. Peptides used previously to interfere with NSF binding also antagonize GluR2-AP2 interaction. Using GluR2 mutants and peptide variants that dissociate NSF and AP2 interaction, we find that AP2 is involved specifically in NMDA receptor-induced (but not ligand-dependent) internalization of AMPA receptors, and is essential for hippocampal long-term depression (LTD). NSF function, on the other hand, is needed to maintain synaptic AMPA receptor responses, but is not directly required for NMDA receptor-mediated internalization and LTD.
Author List
Lee SH, Liu L, Wang YT, Sheng MAuthor
Sang H. Lee PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptor Protein Complex 2Animals
Carrier Proteins
Cell Membrane
Endocytosis
Excitatory Amino Acid Agonists
Excitatory Postsynaptic Potentials
Hippocampus
Long-Term Synaptic Depression
N-Ethylmaleimide-Sensitive Proteins
Neurons
Peptide Fragments
Protein Transport
Rats
Rats, Sprague-Dawley
Receptors, AMPA
Synapses
Synaptic Transmission
Vesicular Transport Proteins
