| First Author | Tomita S | Year | 2007 |
| Journal | Proc Natl Acad Sci U S A | Volume | 104 |
| Issue | 47 | Pages | 18784-8 |
| PubMed ID | 18000041 | Mgi Jnum | J:127599 |
| Mgi Id | MGI:3763972 | Doi | 10.1073/pnas.0708970104 |
| Citation | Tomita S, et al. (2007) AMPA receptors and stargazin-like transmembrane AMPA receptor-regulatory proteins mediate hippocampal kainate neurotoxicity. Proc Natl Acad Sci U S A 104(47):18784-8 |
| abstractText | Naturally occurring glutamate analogs, such as kainate and domoate, which cause excitotoxic shellfish poisoning, induce nondesensitizing responses at neuronal alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. In addition to acting on AMPA receptors, kainate and domoate also activate high-affinity kainate-type glutamate receptors. The receptor type that mediates their neurotoxicity remains uncertain. Here, we show that the transmembrane AMPA receptor-associated protein (TARP) gamma-2 (or stargazin) and the related TARP gamma-8 augment responses to kainate and domoate by making these neurotoxins more potent and more efficacious AMPA receptor agonists. Genetic deletion of hippocampal enriched gamma-8 selectively abolishes sustained depolarizations in hippocampus mediated by kainate activation of AMPA receptors. gamma-8 knockout mice display typical kainate-induced seizures; however, the associated neuronal cell death in the hippocampus is attenuated in mice lacking gamma-8. This work decisively demonstrates that TARP-associated AMPA receptors mediate kainate neurotoxicity and identifies TARPs as targets for modulating neurotoxic properties of AMPA receptors. |
