Bidirectional Regulation of Kainate Receptor Surface Expression in Hippocampal Neurons
Abstract
Kainate receptors (KARs) are crucial for the regulation of both excitatory and inhibitory neurotransmission, but little is known regarding the mechanisms controlling KAR surface expression. We used super ecliptic pHluorin (SEP)-tagged KAR subunit GluR6a to investigate real-time changes in KAR surface expression in hippocampal neurons. Sindbis virus-expressed SEP-GluR6 subunits efficiently co-assembled with native KAR subunits to form heteromeric receptors. Diffuse surface-expressed dendritic SEP-GluR6 is rapidly internalized following either N-methyl-d-aspartate or kainate application. Sustained kainate or transient N-methyl-d-aspartate application resulted in a slow decrease of base-line surface KAR levels. Surprisingly, however, following the initial loss of surface receptors, a short kainate application caused a long lasting increase in surface-expressed KARs to levels significantly greater than those prior to the agonist challenge. These data suggest that after initial endocytosis, transient agonist activation evokes increased KAR exocytosis and reveal that KAR surface expression is bidirectionally regulated. This process may provide a mechanism for hippocampal neurons to differentially adapt their physiological responses to changes in synaptic activation and extrasynaptic glutamate concentration.
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BibTeX
@article{martin2026bidirectional,
title = {{Bidirectional Regulation of Kainate Receptor Surface Expression in Hippocampal Neurons}},
author = {Stéphane Martin and Tristan Bouschet and Emma Jenkins and Atsushi Nishimune and Jeremy Henley},
journal = {Journal of Biological Chemistry},
year = {2026},
month = sep,
doi = {10.1074/jbc.m806447200},
url = {https://hal.science/hal-05745099v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Bidirectional Regulation of Kainate Receptor Surface Expression in Hippocampal Neurons
AU - Stéphane Martin
AU - Tristan Bouschet
AU - Emma Jenkins
AU - Atsushi Nishimune
AU - Jeremy Henley
PY - 2026
DA - 2026/09/10
JO - Journal of Biological Chemistry
DO - 10.1074/jbc.m806447200
UR - https://hal.science/hal-05745099v1
AB - Kainate receptors (KARs) are crucial for the regulation of both excitatory and inhibitory neurotransmission, but little is known regarding the mechanisms controlling KAR surface expression. We used super ecliptic pHluorin (SEP)-tagged KAR subunit GluR6a to investigate real-time changes in KAR surface expression in hippocampal neurons. Sindbis virus-expressed SEP-GluR6 subunits efficiently co-assembled with native KAR subunits to form heteromeric receptors. Diffuse surface-expressed dendritic SEP-GluR6 is rapidly internalized following either N-methyl-d-aspartate or kainate application. Sustained kainate or transient N-methyl-d-aspartate application resulted in a slow decrease of base-line surface KAR levels. Surprisingly, however, following the initial loss of surface receptors, a short kainate application caused a long lasting increase in surface-expressed KARs to levels significantly greater than those prior to the agonist challenge. These data suggest that after initial endocytosis, transient agonist activation evokes increased KAR exocytosis and reveal that KAR surface expression is bidirectionally regulated. This process may provide a mechanism for hippocampal neurons to differentially adapt their physiological responses to changes in synaptic activation and extrasynaptic glutamate concentration.
SN - 0021-9258
SN - 1083-351X
ER -