Clathrin/AP-2 mediate synaptic vesicle reformation from endosome-like vacuoles but are not essential for membrane retrieval at central synapses.
Neuron
; 82(5): 981-8, 2014 Jun 04.
Article
in En
| MEDLINE
| ID: mdl-24908483
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Synapses
/
Synaptic Vesicles
/
Clathrin
/
Coated Pits, Cell-Membrane
/
Adaptor Protein Complex 2
/
Endocytosis
/
Hippocampus
Limits:
Animals
Language:
En
Journal:
Neuron
Journal subject:
NEUROLOGIA
Year:
2014
Type:
Article
Affiliation country:
Germany