Stargazing from a new vantage--TARP modulation of AMPA receptor pharmacology.

摘要

An extensive body of molecular, biochemical and biophysical evidence has firmly established that members of the transmembrane AMPA receptor regulatory protein (TARP) family are AMPA receptor (AMPAR) auxiliary subunits and the dominant modulators of their trafficking and function in the brain. Aside from their role in membrane trafficking and synaptic targeting, TARPs have potent and far-reaching effects on AMPAR gating and pharmacology. TARP family members, such as the canonical TARP y-2 (or stargazin), have been shown to predominantly display salutary effects on AMPAR function, e.g. by slowing desensitization and deactivation kinetics and increasing mean channel conductance. In addition, TARPs can enhance the affinity of AMPARs to their full agonist glutamate, allow partial agonists (i.e. ones that induce submaximal channel activation at saturating concentrations) to act as full agonists and well-known competitive antagonists to behave as partial agonists (Milstein & Nicoll, 2008).