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This Article Full Text Full Text (PDF) All Versions of this Article: 585/3/681    most recent jphysiol.2007.139022v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Granseth, B. Articles by Lagnado, L. Search for Related Content PubMed PubMed Citation Articles by Granseth, B. Articles by Lagnado, L. Related Collections Review articles

¹ MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK

The maintenance of synaptic transmission requires that vesicles are recycled after releasing neurotransmitter. Several modes of retrieval have been proposed to operate at small synaptic terminals of central neurons, but the relative importance of these has been controversial. It is established that synaptic vesicles can collapse on fusion and the machinery for retrieving this membrane by clathrin-mediated endocytosis (CME) is enriched in the presynaptic terminal. But it has also been suggested that the majority of vesicles released by physiological stimulation are recycled by a second, faster mechanism called ‘kiss-and-run’, which operates in 1 s or less to retrieve a vesicle before it has collapsed. The most recent evidence argues against the occurrence of ‘kiss-and-run’ in hippocampal synapses. First, an improved fluorescent reporter of exocytosis (sypHy), indicates that only a slow mode of endocytosis ( = 15 s) operates when vesicle fusion is triggered by a single nerve impulse or short burst. Second, this retrieval mechanism is blocked by overexpressing the C-terminal fragment of AP180 or by knockdown of clathrin using RNAi. Third, vesicle fusion is associated with the movement of clathrin and vesicle proteins out of the synapse into the neighbouring axon. These observations indicate that clathrin-mediated endocytosis is the major, if not exclusive, mechanism of retrieval in small hippocampal synapses.

(Received 19 June 2007; accepted after revision 26 June 2007; first published online 28 June 2007)
Corresponding author L. Lagnado: MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK. Email: ll1{at}mrc-lmb.cam.ac.uk

B. Granseth and B. Odermatt contributed equally to this work.

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