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. ISSN 0028-3908

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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.

Item Type: Article
Additional Information: The funders are: Academy of Finland,Sigrid Juselius Foundation (Finland) and the Finnish Cultural Foundation
Uncontrolled Keywords: AMPA –receptor, GluA4, silent synapse, development, synaptic targeting;
Subjects: University of Westminster > Science and Technology
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Date Deposited: 29 Apr 2016 14:52
Last Modified: 05 May 2017 22:02

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