title: Regulation of AMPA receptor-mediated synaptic transmission by clathrin-dependent receptor internalization.
abstract: Redistribution of postsynaptic AMPA- (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-) subtype glutamate receptors may regulate synaptic strength at glutamatergic synapses, but the mediation of the redistribution is poorly understood. We show that AMPA receptors underwent clathrin-dependent endocytosis, which was accelerated by insulin in a GluR2 subunit-dependent manner. Insulin-stimulated endocytosis rapidly decreased AMPA receptor numbers in the plasma membrane, resulting in long-term depression (LTD) of AMPA receptor-mediated synaptic transmission in hippocampal CA1 neurons. Moreover, insulin-induced LTD and low-frequency stimulation-(LFS-) induced homosynaptic CA1 LTD were found to be mutually occlusive and were both blocked by inhibiting postsynaptic clathrin-mediated endocytosis. Thus, controlling postsynaptic receptor numbers through endocytosis may be an important mechanism underlying synaptic plasticity in the mammalian CNS.
authors.affiliation: Division of Pathology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: H Y
authors.initials: HY
authors.lastname: Man
authors.forename: J W
authors.initials: JW
authors.lastname: Lin
authors.forename: W H
authors.initials: WH
authors.lastname: Ju
authors.forename: G
authors.initials: G
authors.lastname: Ahmadian
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: L E
authors.initials: LE
authors.lastname: Becker
authors.forename: M
authors.initials: M
authors.lastname: Sheng
authors.forename: Y T
authors.initials: YT
authors.lastname: Wang
mesh_terms: D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D002460:Cell Line; D002966:Clathrin / Q000502:physiology*; D003034:Coated Pits, Cell-Membrane / Q000502:physiology; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000166:cytology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000737:chemistry / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D013569:Synapses / Q000737:chemistry / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D002966:Clathrin; D007004:Hypoglycemic Agents; D007328:Insulin; D008565:Membrane Proteins; D018091:Receptors, AMPA; D011956:Receptors, Cell Surface; C104722:glutamate receptor ionotropic, AMPA 2