Building of AMPA‐type glutamate receptors in the endoplasmic reticulum and its implication for excitatory neurotransmission. (21st August 2020)

• Record Type: Journal Article
• Authors: Schwenk, Jochen; Fakler, Bernd
• Is Part Of: Journal of physiology. Volume 599:Number 10(2021)
• Page Start: 2639
• Page End: 2653
• Publication Date: 2020-08-21
• Subjects: ABHD6 -- AMPA‐type glutamate receptors -- assembly -- biogenesis -- CNIH -- complex formation -- cornichon -- endoplasmic reticulum -- FRRS1l -- intellectual disability -- interactome -- synaptic plasticity -- synaptic transmission -- TARP; Physiology -- Periodicals; 612.005
• DOI: 10.1113/JP279025
• Languages: English
• ISSNs: 0022-3751

Abstract

Abstract: AMPA‐type glutamate receptors (AMPARs), the key elements of fast excitatory neurotransmission in the brain, are receptor ion channels whose core is assembled from pore‐forming and three distinct types of auxiliary subunits. While it is well established that this assembly occurs in the endoplasmic reticulum (ER), it has remained largely enigmatic how this receptor‐building happens. Here we review recent findings on the biogenesis of AMPARs in native neurons as a multistep production line that is defined and operated by distinct ER‐resident helper proteins, and we discuss how impairment of these operators by mutations or targeted gene‐inactivation leads to severe phenotypes in both humans and rodents. We suggest that the recent data on AMPAR biogenesis provide new insights into a process that is key to the formation and operation of excitatory synapses and their activity‐dependent dynamics, as well as for the operation of the mammalian brain under normal and pathological conditions. Abstract : Abstract figure legend Assembly of AMPARs occurs in the endoplasmic reticulum (ER). Recent work has unravelled this biogenesis as a multistep assembly line that is defined and operated by a distinct set of helper proteins and that controls the number and composition of AMPARs in excitatory synapses.