Article abstract
Nature Neuroscience 12, 888 - 896 (2009)
Published online: 21 June 2009 | Corrected online: 9 July 2009 | doi:10.1038/nn.2340
Roles of stargazin and phosphorylation in the control of AMPA receptor subcellular distribution
Helmut W Kessels1,2, Charles D Kopec1,2, Matthew E Klein1,2 & Roberto Malinow1,2
Abstract
Understanding how the subcellular fate of newly synthesized AMPA receptors (AMPARs) is controlled is important for elucidating the mechanisms of neuronal function. We examined the effect of increased synthesis of AMPAR subunits on their subcellular distribution in rat hippocampal neurons. Virally expressed AMPAR subunits (GluR1 or GluR2) accumulated in cell bodies and replaced endogenous dendritic AMPAR with little effect on total dendritic amounts and caused no change in synaptic transmission. Coexpressing stargazin (STG) or mimicking GluR1 phosphorylation enhanced dendritic GluR1 levels by protecting GluR1 from lysosomal degradation. However, STG interaction or GluR1 phosphorylation did not increase surface or synaptic GluR1 levels. Unlike GluR1, STG did not protect GluR2 from lysosomal degradation or increase dendritic GluR2 levels. In general, AMPAR surface levels, and not intracellular amounts, correlated strongly with synaptic levels. Our results suggest that AMPAR surface expression, but not its intracellular production or accumulation, is critical for regulating synaptic transmission.
- Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
- Present addresses: Department of Neuroscience, University of California, San Diego, La Jolla, California, USA (H.W.K., M.E.K. and R.M.); Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA (C.D.K.).
Correspondence to: Roberto Malinow1,2 e-mail: rmalinow@ucsd.edu
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