Postsynaptic VAMP/Synaptobrevin Facilitates Differential Vesicle Trafficking of GluA1 and GluA2 AMPA Receptor Subunits.
Vertebrate organisms adapt to a continuously changing environment by regulating the strength of synaptic connections between brain cells. Excitatory synapses are believed to increase their strength by vesicular insertion of transmitter glutamate receptors into the postsynaptic plasma membrane. These vesicles, however, have never been demonstrated or characterized. For the first time, we show the presence of small vesicles in postsynaptic spines, often closely adjacent to the plasma membrane and PSD (postsynaptic density). We demonstrate that they harbor vesicle-associated membrane protein 2 (VAMP2/synaptobrevin-2) and glutamate receptor subunit 1 (GluA1). Disrupting VAMP2 by tetanus toxin treatment reduces the concentration of GluA1 in the postsynaptic plasma membrane. GluA1/VAMP2-containing vesicles, but not GluA2/VAMP2-vesicles, are concentrated in postsynaptic spines relative to dendrites. Our results indicate that small postsynaptic vesicles containing GluA1 are inserted directly into the spine plasma membrane through a VAMP2-dependent mechanism.
Laboratory for Synaptic Plasticity, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Science, University of Oslo, P.O. Box 1105 Blindern, 0317 Oslo, Norway.
Suleman
S
Hussain
Laboratory for Synaptic Plasticity, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Science, University of Oslo, P.O. Box 1105 Blindern, 0317 Oslo, Norway.
Svend
S
Davanger
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology; D018942:Macrolides / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D013572:Synaptic Vesicles / Q000502:physiology*; D013744:Tetanus Toxin / Q000494:pharmacology; D050988:Vesicle-Associated Membrane Protein 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D004791:Enzyme Inhibitors; D018942:Macrolides; D009498:Neurotoxins; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D013744:Tetanus Toxin; D050988:Vesicle-Associated Membrane Protein 2; C040929:bafilomycin A1; C104722:glutamate receptor ionotropic, AMPA 2