Molecular mechanisms controlling synaptic recruitment of GluA4 subunit-containing AMPAreceptors

Luchkina, N.V., Coleman, S.K., Huupponen, J., Cai, C., Kivisto, A., Taira, T., Keinanen, K. and Lauri, S.E. 2017. Molecular mechanisms controlling synaptic recruitment of GluA4 subunit-containing AMPAreceptors. Neuropharmacology. 112 (Part A), pp. 46-56. doi:10.1016/j.neuropharm.2016.04.049

TitleMolecular mechanisms controlling synaptic recruitment of GluA4 subunit-containing AMPAreceptors
AuthorsLuchkina, N.V., Coleman, S.K., Huupponen, J., Cai, C., Kivisto, A., Taira, T., Keinanen, K. and Lauri, S.E.
Abstract

Synaptic recruitment of AMPA receptors (AMPARs) represents a key postsynaptic mechanism
driving functional development and maturation of glutamatergic synapses. At immature
hippocampal synapses, PKA-driven synaptic insertion of GluA4 is the predominant mechanism for
synaptic reinforcement. However, the physiological significance and molecular determinants of this
developmentally restricted form of plasticity are not known. Here we show that PKA activation leads
to insertion of GluA4 to synaptic sites with initially weak or silent AMPAR-mediated transmission.
This effect depends on a novel mechanism involving the extreme C-terminal end of GluA4, which
interacts with the membrane proximal region of the C-terminal domain to control GluA4 trafficking.
In the absence of GluA4, strengthening of AMPAR-mediated transmission during postnatal
development was significantly delayed. These data suggest that the GluA4-mediated activation of
silent synapses is a critical mechanism facilitating the functional maturation of glutamatergic
circuitry during the critical period of experience-dependent fine-tuning.

KeywordsAMPA –receptor, GluA4, silent synapse, development, synaptic targeting
JournalNeuropharmacology
Journal citation112 (Part A), pp. 46-56
ISSN0028-3908
Year2017
PublisherElsevier
Accepted author manuscriptLuchkina et al 2016_FINAL Accepted version.pdf
Digital Object Identifier (DOI)doi:10.1016/j.neuropharm.2016.04.049
Publication dates
Published in printJan 2017
Published online05 May 2016
Published05 May 2016

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