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AMPA-receptor specific biogenesis complexes control synaptic transmission and intellectual ability

Author

Listed:
  • Aline Brechet

    (Institute of Physiology, Faculty of Medicine, University of Freiburg)

  • Rebecca Buchert

    (Institute of Human Genetics, University of Erlangen
    Present address: Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen 72076, Germany)

  • Jochen Schwenk

    (Institute of Physiology, Faculty of Medicine, University of Freiburg
    Center for Biological Signaling Studies (BIOSS))

  • Sami Boudkkazi

    (Institute of Physiology, Faculty of Medicine, University of Freiburg)

  • Gerd Zolles

    (Institute of Physiology, Faculty of Medicine, University of Freiburg)

  • Karine Siquier-Pernet

    (INSERM UMR 1163, Paris-Descartes-Sorbonne Paris Cité University, Institut IMAGINE, Necker-Enfants Malades Hospital)

  • Irene Schaber

    (Institute of Physiology, Faculty of Medicine, University of Freiburg)

  • Wolfgang Bildl

    (Institute of Physiology, Faculty of Medicine, University of Freiburg)

  • Abdelkrim Saadi

    (Etablissement Hospitalier Specialisé de Benaknoun)

  • Christine Bole-Feysot

    (INSERM UMR 1163, Paris-Descartes-Sorbonne Paris Cité University, Institut IMAGINE, Necker-Enfants Malades Hospital)

  • Patrick Nitschke

    (INSERM UMR 1163, Paris-Descartes-Sorbonne Paris Cité University, Institut IMAGINE, Necker-Enfants Malades Hospital)

  • Andre Reis

    (Institute of Human Genetics, University of Erlangen)

  • Heinrich Sticht

    (Institute of Biochemistry, Emil-Fischer Center)

  • Nouriya Al-Sanna’a

    (Dharan Health Center)

  • Arndt Rolfs

    (Center for Biological Signaling Studies (BIOSS)
    Albrecht-Kossel-Institute for Neuroregeneration, Medical University Rostock)

  • Akos Kulik

    (Institute of Physiology, Faculty of Medicine, University of Freiburg
    Center for Biological Signaling Studies (BIOSS))

  • Uwe Schulte

    (Institute of Physiology, Faculty of Medicine, University of Freiburg
    Center for Biological Signaling Studies (BIOSS)
    Logopharm GmbH)

  • Laurence Colleaux

    (INSERM UMR 1163, Paris-Descartes-Sorbonne Paris Cité University, Institut IMAGINE, Necker-Enfants Malades Hospital)

  • Rami Abou Jamra

    (Institute of Human Genetics, University of Erlangen
    Institute of Human Genetics, University of Leipzig Hospitals and Clinics)

  • Bernd Fakler

    (Institute of Physiology, Faculty of Medicine, University of Freiburg
    Center for Biological Signaling Studies (BIOSS))

Abstract

AMPA-type glutamate receptors (AMPARs), key elements in excitatory neurotransmission in the brain, are macromolecular complexes whose properties and cellular functions are determined by the co-assembled constituents of their proteome. Here we identify AMPAR complexes that transiently form in the endoplasmic reticulum (ER) and lack the core-subunits typical for AMPARs in the plasma membrane. Central components of these ER AMPARs are the proteome constituents FRRS1l (C9orf4) and CPT1c that specifically and cooperatively bind to the pore-forming GluA1-4 proteins of AMPARs. Bi-allelic mutations in the human FRRS1L gene are shown to cause severe intellectual disability with cognitive impairment, speech delay and epileptic activity. Virus-directed deletion or overexpression of FRRS1l strongly impact synaptic transmission in adult rat brain by decreasing or increasing the number of AMPARs in synapses and extra-synaptic sites. Our results provide insight into the early biogenesis of AMPARs and demonstrate its pronounced impact on synaptic transmission and brain function.

Suggested Citation

  • Aline Brechet & Rebecca Buchert & Jochen Schwenk & Sami Boudkkazi & Gerd Zolles & Karine Siquier-Pernet & Irene Schaber & Wolfgang Bildl & Abdelkrim Saadi & Christine Bole-Feysot & Patrick Nitschke & , 2017. "AMPA-receptor specific biogenesis complexes control synaptic transmission and intellectual ability," Nature Communications, Nature, vol. 8(1), pages 1-14, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15910
    DOI: 10.1038/ncomms15910
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