NEUROSCIENCE Stargazin, Traffic Cop and Gate Keeper

Stargazin is best known for its role in trafficking AMPA-type glutamate receptors. Delivery of these cation channels to synapses in response to synaptic activity is one mechanism for increasing synaptic strength. Tomita et al. report that stargazin not only traffics AMPA receptors but also stays associated with the receptors and alters channel properties, including ligand sensitivity, gating, and conductance. Using injected oocytes and transfected cells, the authors showed that the first extracellular domain of stargazin, a tetraspanin membrane protein, was responsible for increasing the responsiveness of the receptor to kainate, decreasing the desensitization to glutamate, and increasing the frequency of occurrence of large conductance channel opening events. To substantiate a positive role for stargazin in native cells (hippocampal slice preparations), the authors overexpressed a dominant-negative chimeric protein that could traffic AMPA receptors but not alter their channel properties and showed that the presence of this chimera increased the rate of decay of miniature excitatory postsynaptic currents (mEPSCs) and decreased the peak amplitude. These new roles for stargazin have profound impacts on the meaning of experiments performed in the absence of this protein and lead to questions about whether stargazin itself can be regulated, thereby providing another mechanism for control of synaptic plasticity (see Kristensen and Traynelis).

S. Tomita, H. Adesnik, M. Sekiguchi, W. Zhang, K. Wada, J. R. Howe, R. A. Nicoll, D. S. Bredt, Stargazin modulates AMPA receptor gating and trafficking by distinct domains. Nature 435, 1052-1058 (2005). [PubMed]

A. S. Kristensen, S. F. Traynelis, Neuroscience: An intrusive chaperone. Nature 435, 1042-1043 (2005). [PubMed]

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PERSPECTIVES
STKE Perspectives
AMPA Receptors Do the Electric Slide

Sunita deSouza and Edward B. Ziff (29 October 2002)
Sci. STKE 2002 (156), pe45. [DOI: 10.1126/scisignal.1562002pe45]
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