Distinct molecular mechanisms and divergent endocytotic pathways of AMPA receptor internalization. Nat Neurosci 2000 Dec;3(12):1282-90
Date
12/02/2000Pubmed ID
11100149DOI
10.1038/81814Scopus ID
2-s2.0-0033695663 (requires institutional sign-in at Scopus site) 418 CitationsAbstract
Internalization of postsynaptic AMPA receptors depresses excitatory transmission, but the underlying dynamics and mechanisms of this process are unclear. Using immunofluorescence and surface biotinylation, we characterized and quantified basal and regulated AMPA receptor endocytosis in cultured hippocampal neurons, in response to synaptic activity, AMPA and insulin. AMPA-induced AMPA receptor internalization is mediated in part by secondary activation of voltage-dependent calcium channels, and in part by ligand binding independent of receptor activation. Although both require dynamin, insulin- and AMPA-induced AMPA receptor internalization are differentially dependent on protein phosphatases and sequence determinants within the cytoplasmic tails of GluR1 and GluR2 subunits. AMPA receptors internalized in response to AMPA stimulation enter a recycling endosome system, whereas those internalized in response to insulin diverge into a distinct compartment. Thus, the molecular mechanisms and intracellular sorting of AMPA receptors are diverse, and depend on the internalizing stimulus.
Author List
Lin JW, Ju W, Foster K, Lee SH, Ahmadian G, Wyszynski M, 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
AnimalsCalcineurin
Calcium Signaling
Cells, Cultured
Dynamins
Endocytosis
GTP Phosphohydrolases
Hippocampus
Insulin
Neurons
Protein Transport
Rats
Rats, Sprague-Dawley
Receptors, AMPA
Signal Transduction
Synaptic Transmission
Time Factors
