Stoichiometry of AMPA receptors measured by single molecule imaging

Abstract: AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors are ionotropic glutamate receptors that conduct fast excitatory transmission at the post-synaptic membrane of neurons. AMPA receptors are tetramers composed of four types of subunits, GluA1-4. On the neuronal membrane, they associate with many auxiliary subunits to form larger receptor complexes. The subunit composition of both the core and auxiliary subunits in the complex determine the functionality and trafficking of AMPA receptors. Although the physiology of AMPA receptors is extensively studied, the rules governing the subunit assembly remain elusive. Here, we employ single molecule fluorescence imaging to investigate the assembly of AMPA receptor complexes at the membrane of oocytes of the clawed frog Xenopus laevis. We find that in the GluA1/A2 heteromeric AMPA receptors, 2:2 stoichiometry is strongly preferred. However, it is not the fixed stoichiometry because we also find that 3:1 stoichiometry exists, but is smaller amounts than expected from random assembly. The auxiliary subunits γ-2 and GSG1L (Germ Cell-Specific Gene 1-Like) have four binding sites at one AMPA receptor when expressed alone with GluA1. When co-expressing γ-2 and GSG1L, we observe that they compete for binding to the receptor, and the binding strength of the two subunits is similar. These data reveal the subunit composition of AMPA receptor complexes and suggest possible regulation mechanism by the subunits, thus furthering the understanding of synaptic integration in the central nervous system

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch
Notes
Universität Freiburg, Dissertation, 2018

Keyword
Stoichiometry

Event
Veröffentlichung
(where)
Freiburg
(who)
Universität
(when)
2018
Creator
Contributor

DOI
10.6094/UNIFR/15779
URN
urn:nbn:de:bsz:25-freidok-157797
Rights
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Last update
14.08.2025, 10:56 AM CEST

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Time of origin

  • 2018

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