Functional comparison of the effects of TARPs and cornichons on AMPA receptor trafficking and gating

Abstract

Glutamate receptors of the AMPA subtype (AMPARs) mediate fast synaptic transmission in the brain. These ionotropic receptors rely on auxiliary subunits known as transmembrane AMPAR regulatory proteins (TARPs) for both trafficking and gating. Recently, a second family of AMPAR binding proteins, referred to as cornichons, were identified and also proposed to function as auxiliary subunits. Cornichons are transmembrane proteins that modulate AMPAR function in expression systems much like TARPs. In the present study we compare the role of cornichons in controlling AMPA receptor function in neurons and HEK cells to that of TARPs. Cornichons mimic some, but not all, of the actions of TARPs in HEK cells; their role in neurons, however, is more limited. Although expressed cornichons can affect the trafficking of AMPARs, they were not detected on the surface of neurons and failed to alter the kinetics of endogenous AMPARs. This neuronal role is more consistent with that of an endoplasmic reticulum (ER) chaperone rather than a bona fide auxiliary subunit.stargazin | synapse | auxiliary subunit | hippocampus

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

“…The dissociation and culture of cerebellar granule neurons were performed following the protocol provided in previous work (12,37). Whole-cell patchclamp recordings were made 8-10 d in vitro (DIV) as described in previous reports (12,37,38). SI Materials and Methods provides more details.…”

Regulation of Metabotropic Glutamate Receptor 7 (mGluR7) Internalization and Surface Expression by Ser/Thr Protein Phosphatase 1

“…Surface Receptor Biotinylation Assay-Cell surface biotinylation was performed as described previously (14,15). Briefly, primary cultured cortical neurons (days in vitro 14) were treated with 50 nM okadaic acid or dimethyl sulfoxide for 45 min at 37°C, and washed three times with ice-cold PBS containing 1 mM MgCl 2 and 0.1 mM CaCl 2 (PBSϩϩ).…”

“…Together, these data demonstrate that Ser-862 of mGluR7 is dephosphorylated specifically by PP1. [12][13][14] were incubated with the indicated concentrations of okadaic acid at 37°C for 45 min. Ser-862 phosphorylation of mGluR7, total expression of mGluR7, and expression of tubulin were evaluated by Western blot (WB) analysis.…”

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

“…In particular, CNIH (cornichon) proteins modulate surface trafficking of AMPA receptors and channel gating (11)(12)(13). CNIH-2 is present in multiple brain regions with high levels of expression occurring in the hippocampus and low levels of expression in the cerebellum, particularly within the Purkinje neuron population (12,13). We assessed the effects of CNIH-2 on [ 3 H]-LY450295 binding.…”

“…In addition to the principal GluA subunits, neuronal AMPA receptors typically contain auxiliary transmembrane AMPA receptor regulatory protein (TARPs) 2 subunits (4,5), which enhance receptor trafficking (6) and modulate channel gating (7)(8)(9)(10). Neuronal AMPA receptors may also associate with other transmembrane proteins, including CNIH (cornichon) proteins and CKAMP44, which can further modulate receptor trafficking and channel function (11)(12)(13)(14). AMPA receptors play fundamental roles in controlling behavior, learning, and memory; dysfunction of these receptors likely underlies a variety of neuropsychiatric disorders (15)(16)(17)(18)(19)(20)(21).…”