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The Journal of Neuroscience, October 15, 2003, 23(28):9367-9373
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Cellular/Molecular
Aberrant Formation of Glutamate Receptor Complexes in Hippocampal Neurons of Mice Lacking the GluR2 AMPA Receptor Subunit
Nathalie Sans,1 Bryce Vissel,2,3 Ronald S. Petralia,1 Ya-Xian Wang,1 Kai Chang,1 Gordon A. Royle,2 Chang-Yu Wang,1 Steve O'Gorman,2 Stephen F. Heinemann,2 andRobert J. Wenthold1 1Laboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892-8027, 2Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, and 3Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia
The number and type of receptors present at the postsynaptic membrane determine the response to the neurotransmitter released from the presynaptic terminal. Because most neurons receive multiple and distinct synaptic inputs and contain several different subtypes of receptors stimulated by the same neurotransmitter, the assembly and trafficking of receptors in neurons is a complex process involving many levels of regulation. To investigate the mechanism that neurons use to regulate the assembly of receptor subunits, we studied a GluR2 knock-out mouse. GluR2 is a critical subunit that controls calcium permeability of AMPA receptors and is present in most native AMPA receptors. Our data indicate that in the absence of GluR2, aberrant receptor complexes composed of GluR1 and GluR3 are formed in the hippocampus, and that there is an increased number of homomeric GluR1 and GluR3 receptors. We also show that these homomeric and heteromeric receptors are less efficiently expressed at the synapse. Our results show that GluR2 plays a critical role in controlling the assembly of AMPA receptors, and that the assembly of subunits may reflect the affinity of one subunit for another or the stability of intermediates in the assembly process. Therefore, GluR1 may have a greater preference for GluR2 than it does for GluR3.
Key words: AMPA receptors; assembly; GluR2 knock-out mouse; hippocampus; glutamate receptors; immunoprecipitation
Received June 19, 2003; revised August 27, 2003; accepted August 29, 2003.
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