title: Sorting Nexin 27 regulates basal and activity-dependent trafficking of AMPARs.
abstract: Activity-dependent changes in synaptic strength have long been postulated as cellular correlates of learning and memory. Long-term potentiation (LTP), a well characterized form of synaptic plasticity, is often expressed as an increase in the number of postsynaptic AMPA-type glutamate receptors (AMPARs). Although the precise molecular mechanisms governing LTP remain elusive, this study identifies one member of the sorting nexin family, Sorting Nexin 27 (SNX27), as a critical component in this process. The ability of sorting nexins to bind specific phospholipids as well as their propensity to form protein-protein complexes, points to a role for these proteins in membrane trafficking and protein sorting. Here, we demonstrate that SNX27 binds to AMPARs, and that this interaction is regulated in an activity-dependent manner. Furthermore, we provide evidence that SNX27 is synaptically enriched and its level of expression regulates targeting of AMPARs to the neuronal surface. Loss of SNX27 abolishes recruitment of surface AMPARs during chemical LTP. Collectively, our data suggest a role for SNX27 in modulating synaptic plasticity through regulated interaction with AMPARs.
authors: Solomon H. Snyder Department of Neuroscience,Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and.
authors: Natasha K
authors: NK
authors: Hussain
authors: Solomon H. Snyder Department of Neuroscience,Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and.
authors: Graham H
authors: GH
authors: Diering
authors: Solomon H. Snyder Department of Neuroscience,Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and.
authors: Jonathan
authors: J
authors: Sole
authors: Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane 4072, Queensland, Australia.
authors: Victor
authors: V
authors: Anggono
authors: Solomon H. Snyder Department of Neuroscience,Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and rhuganir@jhmi.edu.
authors: Richard L
authors: RL
authors: Huganir
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D054731:PDZ Domains; D057907:Post-Synaptic Density / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000737:chemistry / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; C477690:Snx27 protein, rat; C104722:glutamate receptor ionotropic, AMPA 2
keywords: PDZ-domain; PX domain; postsynaptic density; proteomics