Subunit-specific Role for the Amino-terminal Domain of AMPA Receptors in Synaptic Targeting

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2017 Jun 21

PMID 28630296

Citations 46

Authors

Javier Diaz-Alonso

Yujiao J Sun

Adam J Granger

Jonathan M Levy

Sabine M Blankenship

Roger A Nicoll

Affiliations

Soon will be listed here.

Abstract

The amino-terminal domain (ATD) of AMPA receptors (AMPARs) accounts for approximately 50% of the protein, yet its functional role, if any, remains a mystery. We have discovered that the translocation of surface GluA1, but not GluA2, AMPAR subunits to the synapse requires the ATD. GluA1A2 heteromers in which the ATD of GluA1 is absent fail to translocate, establishing a critical role of the ATD of GluA1. Inserting GFP into the ATD interferes with the constitutive synaptic trafficking of GluA1, but not GluA2, mimicking the deletion of the ATD. Remarkably, long-term potentiation (LTP) can override the masking effect of the GFP tag. GluA1, but not GluA2, lacking the ATD fails to show LTP. These findings uncover a role for the ATD in subunit-specific synaptic trafficking of AMPARs, both constitutively and during plasticity. How LTP, induced postsynaptically, engages these extracellular trafficking motifs and what specific cleft proteins participate in the process remain to be elucidated.

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