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

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

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Nature Communications. - 8 (2017) , 15910, ISSN: 2041-1723

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2019
• Creator: Bréchet, Aline ; Buchert, Rebecca ; Schwenk, Jochen ; Boudkkazi, Sami ; Zolles, Gerd ; Siquier-Pernet, Karine ; Schaber, Irene ; Bildl, Wolfgang ; Saadi, Abdelkrim ; Bole-Feysot, Christine ; Linsel-Nitschke, Patrick ; Reis, André ; Sticht, Heinrich ; Al-Sannaa, Nouriyah ; Rolfs, Arndt ; Kulik, Akos ; Schulte, Uwe ; Colleaux, Laurence ; Abou Jamra, Rami ; Fakler, Bernd

Further information

• DOI: 10.1038/ncomms15910
• URN: urn:nbn:de:bsz:25-freidok-1390550
• Rights: Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:48 PM CET