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The Journal of Neuroscience, February 15, 2003, 23(4):1151
Studies of NMDA Receptor Function and Stoichiometry with Truncated and Tandem Subunits
Stephanie Schorge and David Colquhoun Pharmacology Department, University College London, London WC1E 6BT, United Kingdom
The subunits that compose eukaryotic glutamate ion channel receptors have three transmembrane domains (TMs) and terminate with intracellular tails that are important for controlling channel expression and localization. Truncation of NMDA receptor subunits before the final TM showed that this TM and intracellular tail region are necessary to form functional channels. However, it is shown here that these truncated subunits may be partially rescued by coexpressing the final TM and tail as a separate protein. The whole-cell currents so produced are somewhat lower than with full-length subunits, and they do not show the sag characteristic of currents from channels containing NR1 and NR2A subunits in the continued presence of an agonist. In addition, these truncated subunits were joined to full-length subunits to generate tandems. The functional expression of these tandems confirmed the tetrameric structure of NMDA receptors and also suggested that the subunits making up NMDA receptors are arranged as a dimer of dimers in the receptors with a 1-1-2-2 orientation of the subunits in the channel, and not in an alternating pattern of subunits around the pore. These results may redirect future studies into the mechanism of binding and gating in these receptors toward schemes including dimers, and may also be relevant to studies of glutamate receptor ion channels in general.
Key words: glutamate receptor; stoichiometry; tandem; dimer; NMDA; ion channel; assembly of subunits
Copyright © 2003 Society for Neuroscience 0270-6474/03/2341151-08$05.00/0
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