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

Aline Brechet, Rebecca Buchert, Jochen Schwenk, Sami Boudkkazi, Gerd Zolles, Karine Siquier-Pernet, Irene Schaber, Wolfgang Bildl, Abdelkrim Saadi, Christine Bole-Feysot, Patrick Nitschke, Andre Reis, Heinrich Sticht, Nouriya Al-Sanna’a, Arndt Rolfs, Akos Kulik, Uwe Schulte, Laurence Colleaux (), Rami Abou Jamra () and Bernd Fakler ()
Additional contact information
Aline Brechet: Institute of Physiology, Faculty of Medicine, University of Freiburg
Rebecca Buchert: Institute of Human Genetics, University of Erlangen
Jochen Schwenk: Institute of Physiology, Faculty of Medicine, University of Freiburg
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)
Akos Kulik: Institute of Physiology, Faculty of Medicine, University of Freiburg
Uwe Schulte: Institute of Physiology, Faculty of Medicine, University of Freiburg
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
Bernd Fakler: Institute of Physiology, Faculty of Medicine, University of Freiburg

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms15910 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15910

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms15910

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().