Abstract
Using a thrombin cleavage assay in cultured hippocampal neurons, we studied the kinetics, regulation and site of AMPA receptor surface delivery. Surface insertion of the GluR1 subunit occurs slowly in basal conditions and is stimulated by NMDA receptor activation and insulin, whereas GluR2 exocytosis is constitutively rapid. Although both subunits ultimately concentrate in synapses, GluR1 and GluR2 show different spatial patterns of surface accumulation, consistent with GluR1 being inserted initially at extrasynaptic sites and GluR2 being inserted more directly at synapses. The spatiotemporal pattern of surface accumulation is determined by the cytoplasmic tails of GluR subunits, and in heteromeric receptors, GluR1 acts dominantly over GluR2. We propose that GluR1 controls the exocytosis and GluR2/3, the recycling and endocytosis of AMPA receptors.
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Acknowledgements
We thank C. Sala, S. Hyoung Lee, M. Wyszynski and Y. Tian Wang for discussions. This work was supported by NIH grant NS 35050 (M.S.). M.S. is Associate Investigator of the Howard Hughes Medical Institute.
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Supplementary Fig.1.
A model for postsynaptic AMPA receptor trafficking.AMPA receptors are represented as heteromers of GluR1/GluR2 or GluR2/GluR3.GluR1 controls the regulated exocytosis of AMPA receptors (acting dominantly in GluR1/GluR2 heteromers).GluR2 mediates the constitutive recycling and regulated endocytosis of AMPA receptors.(See text for details). (GIF 15 kb)
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Passafaro, M., Piëch, V. & Sheng, M. Subunit-specific temporal and spatial patterns of AMPA receptor exocytosis in hippocampal neurons. Nat Neurosci 4, 917–926 (2001). https://doi.org/10.1038/nn0901-917
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DOI: https://doi.org/10.1038/nn0901-917
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