AMPAR/TARP stoichiometry differentially modulates channel properties

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.


Sample-size estimation
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Replicates
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Group allocation
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Additional data files ("source data")
Details on replicates as number of cells or days of experiments are provided in the Source Data Files associated to each figure. In addition, in most of the figures, single data points are plotted together with the mean and median. Data from CGCs are from 7 different cultures as specified on Source Data file - Figure  7. Data was analyzed for possible outliers using the GraphPad Outlier Calculator on line (https://www.graphpad.com/quickcalcs/Grubbs1.cfm) using the Grubbs' test with a significance level of 0.05 (Alpha). If Outliers were encountered, were removed from the data group. Importantly this test was run once per sample group.  • We encourage you to upload relevant additional data files, such as numerical data that are represented as a graph in a figure, or as a summary table • Where provided, these should be in the most useful format, and they can be uploaded as "Source data" files linked to a main figure or table • Include model definition files including the full list of parameters used • Include code used for data analysis (e.g., R, MatLab) • Avoid stating that data files are "available upon request" Please indicate the figures or tables for which source data files have been provided: Associated source data is provided for each figure in Excel files (.xlsx).