TARP redundancy is critical for maintaining AMPA receptor function.

Transmembrane AMPA receptor regulatory proteins are AMPA receptor auxiliary subunits that influence diverse aspects of receptor function. However, the full complement of physiological roles for in vivo remains poorly understood. Here we find that double knock-out mice lacking Tduanyu37s gamma-2 and gamma-3 are profoundly ataxic and fail to thrive. We demonstrate that these Tduanyu37s are critical for the synaptic targeting and kinetics of AMPA receptors in cerebellar Golgi cells, but that either alone is sufficient to fully preserve function. By analyzing the few remaining synaptic AMPA receptors in the gamma-2, gamma-3 double knock-out mice, we unexpectedly find that these Tduanyu37s specify AMPA receptor subunit composition. This study establishes a new role for Tduanyu37s in regulating AMPA receptor assembly and suggests that Tduanyu37s are necessary for proper AMPA receptor localization and function in most, if not all, neurons of the CNS.

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