Tyrosine phosphorylation of GluR2 is required for insulin-stimulated AMPA receptor endocytosis and LTD. EMBO J 2004 Mar 10;23(5):1040-50
Date
02/21/2004Pubmed ID
14976558Pubmed Central ID
PMC380981DOI
10.1038/sj.emboj.7600126Scopus ID
2-s2.0-12144288368 (requires institutional sign-in at Scopus site) 252 CitationsAbstract
The alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) subtype of glutamate receptors is subject to functionally distinct constitutive and regulated clathrin-dependent endocytosis, contributing to various forms of synaptic plasticity. In HEK293 cells transiently expressing GluR1 or GluR2 mutants containing domain deletions or point mutations in their intracellular carboxyl termini (CT), we found that deletion of the first 10 amino acids (834-843) selectively reduced the rate of constitutive AMPA receptor endocytosis, whereas truncation of the last 15 amino acids of the GluR2 CT, or point mutation of the tyrosine residues in this region, only eliminated the regulated (insulin-stimulated) endocytosis. Moreover, in hippocampal slices, both insulin treatment and low-frequency stimulation (LFS) specifically stimulated tyrosine phosphorylation of the GluR2 subunits of native AMPA receptors, and the enhanced phosphorylation appears necessary for both insulin- and LFS-induced long-term depression of AMPA receptor-mediated excitatory postsynaptic currents. Thus, our results demonstrate that constitutive and regulated AMPA receptor endocytosis requires different sequences within GluR CTs and tyrosine phosphorylation of GluR2 CT is required for the regulated AMPA receptor endocytosis and hence the expression of certain forms of synaptic plasticity.
Author List
Ahmadian G, Ju W, Liu L, Wyszynski M, Lee SH, Dunah AW, Taghibiglou C, Wang Y, Lu J, Wong TP, Sheng M, Wang YTAuthor
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
AgingAmino Acid Sequence
Animals
Cells, Cultured
Endocytosis
Hippocampus
Humans
In Vitro Techniques
Insulin
Long-Term Synaptic Depression
Molecular Sequence Data
Mutation
Neurons
Phosphorylation
Phosphotyrosine
Protein Subunits
Rats
Rats, Sprague-Dawley
Receptors, AMPA
Sequence Alignment
Synaptic Transmission
Time Factors
