Clathrin/AP-2 mediate synaptic vesicle reformation from endosome-like vacuoles but are not essential for membrane retrieval at central synapses
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Clathrin/AP-2 mediate synaptic vesicle reformation from endosome-like vacuoles but are not essential for membrane retrieval at central synapses. / Kononenko, Natalia L; Puchkov, Dmytro; Classen, Gala A; Walter, Alexander M; Pechstein, Arndt; Sawade, Linda; Kaempf, Natalie; Trimbuch, Thorsten; Lorenz, Dorothea; Rosenmund, Christian; Maritzen, Tanja; Haucke, Volker.
In: Neuron, Vol. 82, No. 5, 04.06.2014, p. 981-8.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Clathrin/AP-2 mediate synaptic vesicle reformation from endosome-like vacuoles but are not essential for membrane retrieval at central synapses
AU - Kononenko, Natalia L
AU - Puchkov, Dmytro
AU - Classen, Gala A
AU - Walter, Alexander M
AU - Pechstein, Arndt
AU - Sawade, Linda
AU - Kaempf, Natalie
AU - Trimbuch, Thorsten
AU - Lorenz, Dorothea
AU - Rosenmund, Christian
AU - Maritzen, Tanja
AU - Haucke, Volker
N1 - Copyright © 2014 Elsevier Inc. All rights reserved.
PY - 2014/6/4
Y1 - 2014/6/4
N2 - Neurotransmission depends on presynaptic membrane retrieval and local reformation of synaptic vesicles (SVs) at nerve terminals. The mechanisms involved in these processes are highly controversial with evidence being presented for SV membranes being retrieved exclusively via clathrin-mediated endocytosis (CME) from the plasma membrane or via ultrafast endocytosis independent of clathrin. Here we show that clathrin and its major adaptor protein 2 (AP-2) in addition to the plasma membrane operate at internal endosome-like vacuoles to regenerate SVs but are not essential for membrane retrieval. Depletion of clathrin or conditional knockout of AP-2 result in defects in SV reformation and an accumulation of endosome-like vacuoles generated by clathrin-independent endocytosis (CIE) via dynamin 1/3 and endophilin. These results together with theoretical modeling provide a conceptual framework for how synapses capitalize on clathrin-independent membrane retrieval and clathrin/AP-2-mediated SV reformation from endosome-like vacuoles to maintain excitability over a broad range of stimulation frequencies.
AB - Neurotransmission depends on presynaptic membrane retrieval and local reformation of synaptic vesicles (SVs) at nerve terminals. The mechanisms involved in these processes are highly controversial with evidence being presented for SV membranes being retrieved exclusively via clathrin-mediated endocytosis (CME) from the plasma membrane or via ultrafast endocytosis independent of clathrin. Here we show that clathrin and its major adaptor protein 2 (AP-2) in addition to the plasma membrane operate at internal endosome-like vacuoles to regenerate SVs but are not essential for membrane retrieval. Depletion of clathrin or conditional knockout of AP-2 result in defects in SV reformation and an accumulation of endosome-like vacuoles generated by clathrin-independent endocytosis (CIE) via dynamin 1/3 and endophilin. These results together with theoretical modeling provide a conceptual framework for how synapses capitalize on clathrin-independent membrane retrieval and clathrin/AP-2-mediated SV reformation from endosome-like vacuoles to maintain excitability over a broad range of stimulation frequencies.
KW - Adaptor Protein Complex 2/genetics
KW - Animals
KW - Clathrin/genetics
KW - Coated Pits, Cell-Membrane/physiology
KW - Dynamins/metabolism
KW - Endocytosis
KW - Endosomes/physiology
KW - Hippocampus/physiology
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Transgenic
KW - Models, Theoretical
KW - Neurons/physiology
KW - Rats
KW - Synapses/physiology
KW - Synaptic Vesicles/physiology
U2 - 10.1016/j.neuron.2014.05.007
DO - 10.1016/j.neuron.2014.05.007
M3 - Journal article
C2 - 24908483
VL - 82
SP - 981
EP - 988
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 5
ER -
ID: 334036672