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
Hauptverfasser: Voglmaier, Susan M., Kam, Kaiwen, Yang, Hua, Fortin, Doris L., Hua, Zhaolin, Nicoll, Roger A., Edwards, Robert H.
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container_end_page 84
container_issue 1
container_start_page 71
container_title Neuron (Cambridge, Mass.)
container_volume 51
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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