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Dynamic Interaction of Stargazin-like TARPs with Cycling AMPA Receptors at Synapses
Susumu Tomita,1
Masaki Fukata,1
Roger A. Nicoll,1,2
David S. Bredt1*
Abstract:
Activity-dependent plasticity in the brain arises in part fromchanges in the number of synaptic AMPA receptors. Synaptic traffickingof AMPA receptors is controlled by stargazin and homologoustransmembrane AMPA receptor regulatory proteins (TARPs). Wefound that TARPs were stable at the plasma membrane, whereasAMPA receptors were internalized in a glutamate-regulated manner.Interaction with AMPA receptors involved both extra- and intracellulardeterminants of TARPs. Upon binding to glutamate, AMPA receptorsdetached from TARPs. This did not require ion flux or intracellularsecond messengers. This allosteric mechanism for AMPA receptordissociation from TARPs may participate in glutamate-mediatedinternalization of receptors in synaptic plasticity.
1 Department of Physiology, University of California, San Francisco, San Francisco, CA 941432140, USA. 2 Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 941432140, USA.
* To whom correspondence should be addressed. E-mail: bredt{at}itsa.ucsf.edu
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