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AMPAR/TARP stoichiometry differentially modulates channel properties
Federico Miguez-Cabello1, Nuria Sánchez-Fernández1, Natalia Yefimenko1
1Laboratori de Neurofisiologia, Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.
Elife
|May 27, 2020
Summary
The stoichiometry of TARP γ2 binding to AMPARs significantly impacts channel properties, with full saturation required for key TARP-induced characteristics. Differences were observed between calcium-permeable and impermeable AMPARs, suggesting two γ2 molecules at cerebellar granule cell receptors.
Area of Science:
- Neuroscience
- Molecular Biology
- Biophysics
Background:
- AMPA receptors (AMPARs) mediate fast synaptic transmission.
- Auxiliary subunits, such as TARPs, modulate AMPAR function.
- The stoichiometric relationship between AMPARs and TARPs is poorly understood.
Purpose of the Study:
- To investigate the stoichiometry-dependent modulation of AMPARs by TARP γ2.
- To explore differences in modulation between calcium-permeable and impermeable AMPARs.
- To determine the stoichiometry of γ2 at endogenous AMPARs in mouse cerebellar granule cells.
Main Methods:
- Electrophysiological recordings of recombinant AMPARs and TARP γ2.
- Mutagenesis studies to assess the role of γ2 positioning.
- Comparison with endogenous AMPAR currents from mouse cerebellar granule cells.
Main Results:
- AMPARs exhibit stoichiometry-dependent modulation by TARP γ2.
- Full saturation with γ2 is necessary for typical TARP-induced channel conductance.
- Distinct stoichiometric modulation patterns exist for calcium-permeable versus impermeable AMPARs.
- γ2 positioning within heteromeric AMPARs influences TARP-dependent features.
- A stoichiometry of two γ2 molecules per somatic AMPAR was inferred in mouse cerebellar granule cells.
Conclusions:
- TARP γ2 stoichiometry critically influences AMPAR channel properties.
- The number and positioning of γ2 subunits are key determinants of AMPAR function.
- Endogenous AMPARs in cerebellar granule cells likely contain two γ2 subunits.
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