title: Postsynaptic complexin controls AMPA receptor exocytosis during LTP.
abstract: Long-term potentiation (LTP) is a compelling synaptic correlate of learning and memory. LTP induction requires NMDA receptor (NMDAR) activation, which triggers SNARE-dependent exocytosis of AMPA receptors (AMPARs). However, the molecular mechanisms mediating AMPAR exocytosis induced by NMDAR activation remain largely unknown. Here, we show that complexin, a protein that regulates neurotransmitter release via binding to SNARE complexes, is essential for AMPAR exocytosis during LTP but not for the constitutive AMPAR exocytosis that maintains basal synaptic strength. The regulated postsynaptic AMPAR exocytosis during LTP requires binding of complexin to SNARE complexes. In hippocampal neurons, presynaptic complexin acts together with synaptotagmin-1 to mediate neurotransmitter release. However, postsynaptic synaptotagmin-1 is not required for complexin-dependent AMPAR exocytosis during LTP. These results suggest a complexin-dependent molecular mechanism for regulating AMPAR delivery to synapses, a mechanism that is surprisingly similar to presynaptic exocytosis but controlled by regulators other than synaptotagmin-1.
authors.affiliation: Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford CA 94305, USA.
authors.forename: Mohiuddin
authors.initials: M
authors.lastname: Ahmad
authors.forename: Jai S
authors.initials: JS
authors.lastname: Polepalli
authors.forename: Debanjan
authors.initials: D
authors.lastname: Goswami
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Yang
authors.forename: Yea Jin
authors.initials: YJ
authors.lastname: Kaeser-Woo
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
authors.forename: Robert C
authors.initials: RC
authors.lastname: Malenka
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005089:Exocytosis / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D057907:Post-Synaptic Density / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D018091:Receptors, AMPA / Q000378:metabolism*; D050600:SNARE Proteins / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D050863:Synaptotagmin I / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D050600:SNARE Proteins; D050863:Synaptotagmin I; C095992:complexin I