Transmembrane AMPA receptor regulatory proteins and AMPA receptor function in the cerebellum

AbstractHeterogeneity among AMPA receptor (AMPAR) subtypes is thought to be one of the key postsynaptic factors giving rise to diversity in excitatory synaptic signaling in the CNS. Recently, compelling evidence has emerged that ancillary AMPAR subunits—the so-called transmembrane AMPA receptor regulatory proteins (TARPs)—also play a vital role in influencing the variety of postsynaptic signaling. This TARP family of molecules controls both trafficking and functional properties of AMPARs at most, if not all, excitatory central synapses. Furthermore, individual TARPs differ in their effects on the biophysical and pharmacological properties of AMPARs. The critical importance of TARPs in synaptic transmission was first revealed in experiments on cerebellar granule cells from stargazer mice. These lack the prototypic TARP stargazin, present in granule cells from wild-type animals, and consequently lack synaptic transmission at the mossy fibre-to-granule cell synapse. Subsequent work has identified many other members of the stargazin family which act as functional TARPs. It has also provided valuable information about specific TARPs present in many central neurons. Because much of the initial work on TARPs was carried out on stargazer granule cells, the important functional properties of TARPs present throughout the cerebellum have received particular attention. Here we discuss some of these recent findings in relation to the main TARPs and the AMPAR subunits identified in cerebellar neurons and glia