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Article Dans Une Revue Nature Communications Année : 2017

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

Résumé

AMPA-type glutamate receptors (AMPARs), key elements in excitatory neuro-transmission 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.
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Dates et versions

hal-02044718 , version 1 (21-02-2019)

Identifiants

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Aline Brechet, Rebecca Buchert, Jochen Schwenk, Sami Boudkkazi, Gerd Zolles, et al.. AMPA-receptor specific biogenesis complexes control synaptic transmission and intellectual ability. Nature Communications, 2017, 8, pp.15910. ⟨10.1038/ncomms15910⟩. ⟨hal-02044718⟩
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