title: Differential vesicular sorting of AMPA and GABAA receptors.
abstract: In mature neurons AMPA receptors cluster at excitatory synapses primarily on dendritic spines, whereas GABAA receptors cluster at inhibitory synapses mainly on the soma and dendritic shafts. The molecular mechanisms underlying the precise sorting of these receptors remain unclear. By directly studying the constitutive exocytic vesicles of AMPA and GABAA receptors in vitro and in vivo, we demonstrate that they are initially sorted into different vesicles in the Golgi apparatus and inserted into distinct domains of the plasma membrane. These insertions are dependent on distinct Rab GTPases and SNARE complexes. The insertion of AMPA receptors requires SNAP25-syntaxin1A/B-VAMP2 complexes, whereas insertion of GABAA receptors relies on SNAP23-syntaxin1A/B-VAMP2 complexes. These SNARE complexes affect surface targeting of AMPA or GABAA receptors and synaptic transmission. Our studies reveal vesicular sorting mechanisms controlling the constitutive exocytosis of AMPA and GABAA receptors, which are critical for the regulation of excitatory and inhibitory responses in neurons.
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
authors.forename: Yi
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Chiu
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
authors.forename: Bian
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218;
authors.forename: Pei-Hsun
authors.initials: PH
authors.lastname: Wu
authors.affiliation: Johns Hopkins University School of Medicine Microscope Facility, Baltimore, MD 21205.
authors.forename: Michael
authors.initials: M
authors.lastname: Delannoy
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
authors.forename: Da-Ting
authors.initials: DT
authors.lastname: Lin
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218;
authors.forename: Denis
authors.initials: D
authors.lastname: Wirtz
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205; rhuganir@jhmi.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005089:Exocytosis; D006056:Golgi Apparatus / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D050827:Syntaxin 1 / Q000378:metabolism; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism
chemical_list: D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D050827:Syntaxin 1; C494706:Vamp2 protein, rat; D050988:Vesicle-Associated Membrane Protein 2
keywords: AMPA receptor; GABAA receptor; SNARE; TIRFM; constitutive exocytosis
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