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

Abstract

Heterogeneity 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.

Na+/K+‐ATPase inhibitor palytoxin enhances vulnerability of cultured cerebellar neurons to domoic acid via sodium‐dependent mechanisms

“…Other possibilities may be considered. The so-called transmembrane AMPA receptor regulatory proteins (TARPs) have recently emerged as a family of proteins which profoundly affects the trafficking and gating of AMPA receptors (see Coombs and Cull-Candy 2009 for a review). TARPs modify many AMPA receptor properties including their single channel conductance, channel kinetics, open probability, sensitivity to polyamines and interaction with agonists and antagonists.…”

Relative contribution of TARPs γ-2 and γ-7 to cerebellar excitatory synaptic transmission and motor behavior

“…Cerebellar granule neurons (CGNs), which express high levels of stargazin, were found to lack surface AMPA-type glutamate receptors (AMPARs) in the stg mouse (3,4). Stargazin not only controls the trafficking of AMPARs, but also controls AMPAR gating (5)(6)(7)(8)(9)(10), indicating that it satisfies all of the criteria of auxiliary subunits. Stargazin is a member of a family of proteins referred to as transmembrane AMPAR regulatory proteins (TARPs) and consists of the following members: canonical type I TARPs (γ-2, γ-3, γ-4, and γ-8) and atypical type II TARPs (γ-5 and γ-7), which differ in their amino acid sequence and uniquely regulate AMPAR trafficking, gating, and neuropharmacology (7).…”

Transmembrane AMPA Receptor Regulatory Proteins and Cornichon-2 Allosterically Regulate AMPA Receptor Antagonists and Potentiators

“…1B). Because GluA2 is incorporated into AMPA receptors across multiple brain regions, we focused on this GluA subunit (37 (4,(41)(42)(43)(44)(45). In particular, stargazin (␥-2) slows AMPA receptor desensitization, augments steady state currents and increases the affinity for both the full agonist glutamate and the partial agonist kainate (7)(8)(9)(10) Fig.…”