Distinct Endocytic Pathways Control the Rate and Extent of Synaptic Vesicle Protein Recycling
Synaptic vesicles have been proposed to form through two mechanisms: one directly from the plasma membrane involving clathrin-dependent endocytosis and the adaptor protein AP2, and the other from an endosomal intermediate mediated by the adaptor AP3. However, the relative role of these two mechanism...
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Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 2006-07, Vol.51 (1), p.71-84 |
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creator | Voglmaier, Susan M. Kam, Kaiwen Yang, Hua Fortin, Doris L. Hua, Zhaolin Nicoll, Roger A. Edwards, Robert H. |
description | Synaptic vesicles have been proposed to form through two mechanisms: one directly from the plasma membrane involving clathrin-dependent endocytosis and the adaptor protein AP2, and the other from an endosomal intermediate mediated by the adaptor AP3. However, the relative role of these two mechanisms in synaptic vesicle recycling has remained unclear. We now find that vesicular glutamate transporter VGLUT1 interacts directly with endophilin, a component of the clathrin-dependent endocytic machinery. In the absence of its interaction with endophilin, VGLUT1 recycles more slowly during prolonged, high-frequency stimulation. Inhibition of the AP3 pathway with brefeldin A rescues the rate of recycling, suggesting a competition between AP2 and -3 pathways, with endophilin recruiting VGLUT1 toward the faster AP2 pathway. After stimulation, however, inhibition of the AP3 pathway prevents the full recovery of VGLUT1 by endocytosis, implicating the AP3 pathway specifically in compensatory endocytosis. |
doi_str_mv | 10.1016/j.neuron.2006.05.027 |
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subjects | Acyltransferases - metabolism Adaptor Protein Complex 2 - metabolism Adaptor Protein Complex 3 - antagonists & inhibitors Adaptor Protein Complex 3 - metabolism Amino Acid Motifs - physiology Animals Brefeldin A - pharmacology CELLBIO Endocytosis Endocytosis - physiology Glutamic Acid - metabolism MOLNEURO Plasma Presynaptic Terminals - metabolism Presynaptic Terminals - ultrastructure Protein Binding - physiology Protein Structure, Tertiary - physiology Protein Synthesis Inhibitors - pharmacology Proteins Rats Rats, Sprague-Dawley Rodents Signal Transduction - drug effects Signal Transduction - physiology Synaptic Vesicles - metabolism Synaptic Vesicles - ultrastructure Vesicular Glutamate Transport Protein 1 - chemistry Vesicular Glutamate Transport Protein 1 - metabolism Vesicular Transport Proteins - metabolism |
title | Distinct Endocytic Pathways Control the Rate and Extent of Synaptic Vesicle Protein Recycling |
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