Dynamic Interaction of Stargazin-like TARPs with Cycling AMPA Receptors at Synapses

Tomita, Susumu
Fukata, Masaki
Nicoll, Roger A.
Bredt, David S.

¹Department of Physiology and ²Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143-2140, USA.

*To whom correspondence should be addressed. E-mail: [email protected]

Supporting Online Material: www.sciencemag.org/cgi/content/full/303/5663/1508/DC1; Materials and Methods; Figs. S1 and S2; References

8 August 2003; accepted 2 February 2004

Science 303(5663):p 1508-1511, March 5, 2004.

Activity-dependent plasticity in the brain arises in part from changes in the number of synaptic AMPA receptors. Synaptic trafficking of AMPA receptors is controlled by stargazin and homologous transmembrane AMPA receptor regulatory proteins (TARPs). We found that TARPs were stable at the plasma membrane, whereas AMPA receptors were internalized in a glutamate-regulated manner. Interaction with AMPA receptors involved both extra- and intracellular determinants of TARPs. Upon binding to glutamate, AMPA receptors detached from TARPs. This did not require ion flux or intracellular second messengers. This allosteric mechanism for AMPA receptor dissociation from TARPs may participate in glutamate-mediated internalization of receptors in synaptic plasticity.