Endocytic Trafficking and Recycling Maintain a Pool of Mobile Surface AMPA Receptors Required for Synaptic Potentiation

At excitatory glutamatergic synapses, postsynaptic endocytic zones (EZs), which are adjacent to the postsynaptic density (PSD), mediate clathrin-dependent endocytosis of surface AMPA receptors (AMPAR) as a first step to receptor recycling or degradation. However, it remains unknown whether receptor...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2009-07, Vol.63 (1), p.92-105
Main Authors: Petrini, Enrica Maria, Lu, Jiuyi, Cognet, Laurent, Lounis, Brahim, Ehlers, Michael D., Choquet, Daniel
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Binding sites
Carrier Proteins - genetics
Carrier Proteins - metabolism
CELLBIO
Cells, Cultured
Clathrin - genetics
Clathrin - metabolism
Dyneins - genetics
Embryo, Mammalian
Endocytosis - physiology
Excitatory Postsynaptic Potentials - genetics
Fluorescence Recovery After Photobleaching - methods
Glycine - pharmacology
Green Fluorescent Proteins - genetics
Hippocampus - cytology
Homer Scaffolding Proteins
Models, Biological
MOLNEURO
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Neurons
Neurons - cytology
Neurons - drug effects
Patch-Clamp Techniques
Protein Transport - drug effects
Protein Transport - genetics
Proteins
Quantum dots
Rats
Rats, Sprague-Dawley
Receptors, AMPA - genetics
Receptors, AMPA - metabolism
SIGNALING
Synapses - drug effects
Synapses - metabolism
Time Factors
Transfection - methods
Wavelet transforms
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Summary:At excitatory glutamatergic synapses, postsynaptic endocytic zones (EZs), which are adjacent to the postsynaptic density (PSD), mediate clathrin-dependent endocytosis of surface AMPA receptors (AMPAR) as a first step to receptor recycling or degradation. However, it remains unknown whether receptor recycling influences AMPAR lateral diffusion and whether EZs are important for the expression of synaptic potentiation. Here, we demonstrate that the presence of both EZs and AMPAR recycling maintain a large pool of mobile AMPARs at synapses. In addition, we find that synaptic potentiation is accompanied by an accumulation and immobilization of AMPARs at synapses resulting from both their exocytosis and stabilization at the PSD. Displacement of EZs from the postsynaptic region impairs the expression of synaptic potentiation by blocking AMPAR recycling. Thus, receptor recycling is crucial for maintaining a mobile population of surface AMPARs that can be delivered to synapses for increases in synaptic strength.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2009.05.025