title: Synaptic activity regulates AMPA receptor trafficking through different recycling pathways.
abstract: Changes in glutamatergic synaptic strength in brain are dependent on AMPA-type glutamate receptor (AMPAR) recycling, which is assumed to occur through a single local pathway. In this study, we present evidence that AMPAR recycling occurs through different pathways regulated by synaptic activity. Without synaptic stimulation, most AMPARs recycled in dynamin-independent endosomes containing the GTPase, Arf6. Few AMPARs recycled in dynamin-dependent endosomes labeled by transferrin receptors (TfRs). AMPAR recycling was blocked by alterations in the GTPase, TC10, which co-localized with Arf6 endosomes. TC10 mutants that reduced AMPAR recycling had no effect on increased AMPAR levels with long-term potentiation (LTP) and little effect on decreased AMPAR levels with long-term depression. However, internalized AMPAR levels in TfR-containing recycling endosomes increased after LTP, indicating increased AMPAR recycling through the dynamin-dependent pathway with synaptic plasticity. LTP-induced AMPAR endocytosis is inconsistent with local recycling as a source of increased surface receptors, suggesting AMPARs are trafficked from other sites.
authors.affiliation: Department of Neurobiology, University of Chicago, Chicago, United States.
authors.forename: Ning
authors.initials: N
authors.lastname: Zheng
authors.affiliation: Department of Neurobiology, University of Chicago, Chicago, United States.
authors.forename: Okunola
authors.initials: O
authors.lastname: Jeyifous
authors.affiliation: Department of Physiology, University of Auckland, Auckland, New Zealand.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Munro
authors.affiliation: Marine Biological Laboratory, Woods Hole, United States.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Montgomery
authors.affiliation: Department of Neurobiology, University of Chicago, Chicago, United States.
authors.forename: William N
authors.initials: WN
authors.lastname: Green
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000502:physiology*; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000096:biosynthesis; D011992:Endosomes / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology; D008856:Microscopy, Fluorescence; D016296:Mutagenesis; D018408:Patch-Clamp Techniques; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D014162:Transfection; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors; D017931:DNA Primers; D018076:DNA, Complementary; D018091:Receptors, AMPA; D020741:rho GTP-Binding Proteins; C503262:Rhoq protein, rat; C000715349:Arf6 protein, rat
keywords: AMPA receptors; LTD; LTP; cell biology; endocytosis; neuroscience; rat; synaptic plasticity