Abstract
The regulation of synaptic AMPA receptors (AMPARs) is critical for excitatory synaptic transmission, synaptic plasticity and the consequent formation of neural circuits during brain development and their modification during learning and memory processes. The number of synaptic AMPARs is regulated through endocytosis, exocytosis and endosomal sorting that results in recycling back to the plasma membrane or degradation in the lysosome. Hence, endo-lysosomal sorting is vitally important in maintaining AMPAR expression at the synapse, and the dynamic regulation of these trafficking events is a key component of synaptic plasticity. A reduction in synaptic strength such as in long-term depression (LTD) involves AMPAR sorting to lysosomes to reduce synaptic AMPAR number, whereas long-term potentiation (LTP) involves an increase in AMPAR recycling to increase the number of AMPARs at synapses. Here, we review our current understanding of the endosomal trafficking routes taken by AMPARs, and the mechanisms involved in AMPAR endosomal sorting, focussing on the numerous AMPAR associated proteins that have been implicated in this complex process. We also discuss how these events are dysregulated in brain disorders.
Highlights
Mechanisms of AMPA Receptor Endosomal SortingThe regulation of synaptic AMPA receptors (AMPARs) is critical for excitatory synaptic transmission, synaptic plasticity and the consequent formation of neural circuits during brain development and their modification during learning and memory processes
AMPA receptors (AMPARs) are ionotropic glutamate receptors that comprise hetero-tetrameric assemblies of subunits GluA1–4
There are 3 possible routes that AMPARs can take from EEs: (1) a recycling path that returns cargo back to the plasma membrane via recycling endosomes (REs; Figure 1—step 2; van der Sluijs and Hoogenraad, 2011); (2) EEs can mature into late endosomes/multivesicular bodies (LEs/MVBs) and subsequently lysosomes to degrade the cargo contained therein (Figure 1—step 4; Hu et al, 2015); (3) cargo can be targeted from EEs back to the biosynthetic machinery for further post-translational modification (PTM; Figure 1—step 3; Hirling, 2009; van der Sluijs and Hoogenraad, 2011; Burd and Cullen, 2014)
Summary
The regulation of synaptic AMPA receptors (AMPARs) is critical for excitatory synaptic transmission, synaptic plasticity and the consequent formation of neural circuits during brain development and their modification during learning and memory processes. The number of synaptic AMPARs is regulated through endocytosis, exocytosis and endosomal sorting that results in recycling back to the plasma membrane or degradation in the lysosome. Endo-lysosomal sorting is vitally important in maintaining AMPAR expression at the synapse, and the dynamic regulation of these trafficking events is a key component of synaptic plasticity. We review our current understanding of the endosomal trafficking routes taken by AMPARs, and the mechanisms involved in AMPAR endosomal sorting, focussing on the numerous AMPAR associated proteins that have been implicated in this complex process.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
