| First Author | Brechet A | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 15910 | PubMed ID | 28675162 |
| Mgi Jnum | J:252025 | Mgi Id | MGI:5921155 |
| Doi | 10.1038/ncomms15910 | Citation | Brechet A, et al. (2017) AMPA-receptor specific biogenesis complexes control synaptic transmission and intellectual ability. Nat Commun 8:15910 |
| abstractText | 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. |
