Logo SFB 746

 

FOR2143


Institute of Physiology
University of Freiburg
Hermann-Herder-Str. 7
79104 Freiburg
Germany
How to find us

Physiology I
N.N.
Kommissarische Leitung:
Prof. Dr. Marlene Bartos

Physiology II
Prof. Dr. Bernd Fakler
Tel. +49 761 203-5176
Fax +49 761 203-5191
[JavaScript Protected Email]

Uni-Logo
You are here: Home News AMPA-receptor specific biogenesis complexes control synaptic transmission and intellectual ability
Document Actions

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

Aline Brechet et al. Nat Commun. 2017; 8:15910. doi: 10.1038/ncomms15910.

Jul 05, 2017

AMPA-type glutamate receptors (AMPARs), key elements in excitatory neurotransmission inthe brain, are macromolecular complexes whose properties and cellular functions are determined by the co-assembled constituents of their proteome. Here we identify AMPARcomplexes 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.

Personal tools