AMPAR/TARP stoichiometry differentially modulates channel properties

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Abstract

AMPARs control fast synaptic communication between neurons and their function relies on auxiliary subunits, which importantly modulate channel properties. Although it has been suggested that AMPARs can bind to TARPs with variable stoichiometry, little is known about the effect that this stoichiometry exerts on certain AMPAR properties. Here we have found that AMPARs show a clear stoichiometry-dependent modulation by the prototypical TARP γ2 although the receptor still needs to be fully saturated with γ2 to show some typical TARP-induced characteristics (i.e. an increase in channel conductance). We also uncovered important differences in the stoichiometric modulation between calcium-permeable and calcium-impermeable AMPARs. Moreover, in heteromeric AMPARs, γ2 positioning in the complex is important to exert certain TARP-dependent features. Finally, by comparing data from recombinant receptors with endogenous AMPAR currents from mouse cerebellar granule cells, we have determined a likely presence of two γ2 molecules at somatic receptors in this cell type.

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All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for all Figures.

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Federico Miguez-Cabello

Biomedicine, University of Barcelona, Barcelona, Spain

Competing interests
The authors declare that no competing interests exist.
Nuria Sánchez-Fernández

Biomedicine, University of Barcelona, Barcelona, Spain

Competing interests
The authors declare that no competing interests exist.
Natalia Yefimenko

Biomedicine, University of Barcelona, Barcelona, Spain

Competing interests
The authors declare that no competing interests exist.
Xavier Gasull

Biomedicine, University of Barcelona, Barcelona, Spain

Competing interests
The authors declare that no competing interests exist.
Esther Gratacòs-Batlle

Biomedicine, University of Barcelona, Barcelona, Spain

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-8093-3713
David Soto

Department of Biomedicine, Medical School, University of Barcelona, Barcelona, Spain

For correspondence
davidsoto@ub.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7995-3805

Funding

Ministerio de Economía y Competitividad (BFU2017-83317-P)

David Soto

Instituto de Salud Carlos III (RD16/0008/0014)

Xavier Gasull

Generalitat de Catalunya (2017SGR737)

Xavier Gasull

Instituto de Salud Carlos III (FIS-PI17/00296)

Xavier Gasull

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The authors state that the animals used in this study were sacrificed following the guidelines of CEEA-UB (Ethical Committee for Animal Research) from University of Barcelona with the license number OB117/16, of which Dr. David Soto is the responsible principal investigator.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.