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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
- Source :
- Neuron. 82(5):981-988
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- SummaryNeurotransmission 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.
- Subjects :
- Dynamins
Endosome
Neuroscience(all)
Adaptor Protein Complex 2
Mice, Transgenic
Endosomes
Endocytosis
Clathrin
Synaptic vesicle
Hippocampus
Exocytosis
Bulk endocytosis
Mice
Animals
Dynamin
Neurons
biology
General Neuroscience
Coated Pits, Cell-Membrane
Models, Theoretical
Cell biology
Rats
Mice, Inbred C57BL
Synapses
biology.protein
Clathrin adaptor proteins
Synaptic Vesicles
Subjects
Details
- ISSN :
- 08966273
- Volume :
- 82
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Neuron
- Accession number :
- edsair.doi.dedup.....afb9de41629c40028a546e9aa41a0565
- Full Text :
- https://doi.org/10.1016/j.neuron.2014.05.007