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

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Brechet A, Buchert R, Schwenk J, Boudkkazi S, Zolles G, Siquier-Pernet K, Schaber I, Bildl W, Saadi A, Bole-Feysot C, Nitschke P, Reis A, Sticht H, Al-Sanna'A N, Rolfs A, Kulik A, Schulte U, Colleaux L, Abou Jamra R, Fakler B
Zeitschrift: Nature Communications
Jahr der Veröffentlichung: 2017
Band: 8
Seitenbereich: 15910
ISSN: 2041-1723


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.



FAU-Autoren / FAU-Herausgeber

Buchert, Rebecca
Lehrstuhl für Humangenetik
Sticht, Heinrich Prof. Dr.
Professur für Bioinformatik


Autor(en) der externen Einrichtung(en)
Albert-Ludwigs-Universität Freiburg
ARAMCO - Dharan Health Center
Hopital Benaknoun
Universität Paris Descartes / Université Paris 5 René Descartes


Zitierweisen

APA:
Brechet, A., Buchert, R., Schwenk, J., Boudkkazi, S., Zolles, G., Siquier-Pernet, K.,... Fakler, B. (2017). AMPA-receptor specific biogenesis complexes control synaptic transmission and intellectual ability. Nature Communications, 8, 15910. https://dx.doi.org/10.1038/ncomms15910

MLA:
Brechet, Aline, et al. "AMPA-receptor specific biogenesis complexes control synaptic transmission and intellectual ability." Nature Communications 8 (2017): 15910.

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Zuletzt aktualisiert 2018-10-10 um 08:21