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Dilation of fusion pores by crowding of SNARE proteins

Title: Dilation of fusion pores by crowding of SNARE proteins
Authors: Wu, Z; Bello, OD; Thiyagarajan, S; Auclair, SM; Vennekate, W; Krishnakumar, SS; O'Shaughnessy, B; Karatekin, E
Source: ELIFE , 6 , Article e22964. (2017)
Publisher Information: ELIFE SCIENCES PUBLICATIONS LTD
Publication Year: 2017
Collection: University College London: UCL Discovery
Description: Hormones and neurotransmitters are released through fluctuating exocytotic fusion pores that can flicker open and shut multiple times. Cargo release and vesicle recycling depend on the fate of the pore, which may reseal or dilate irreversibly. Pore nucleation requires zippering between vesicle-associated v-SNAREs and target membrane t-SNAREs, but the mechanisms governing the subsequent pore dilation are not understood. Here, we probed the dilation of single fusion pores using v-SNARE-reconstituted ~23-nm-diameter discoidal nanolipoprotein particles (vNLPs) as fusion partners with cells ectopically expressing cognate, 'flipped' t-SNAREs. Pore nucleation required a minimum of two v-SNAREs per NLP face, and further increases in v-SNARE copy numbers did not affect nucleation rate. By contrast, the probability of pore dilation increased with increasing v-SNARE copies and was far from saturating at 15 v-SNARE copies per face, the NLP capacity. Our experimental and computational results suggest that SNARE availability may be pivotal in determining whether neurotransmitters or hormones are released through a transient ('kiss and run') or an irreversibly dilating pore (full fusion).
Document Type: article in journal/newspaper
File Description: text
Language: English
Relation: https://discovery.ucl.ac.uk/id/eprint/1557779/
Availability: https://discovery.ucl.ac.uk/id/eprint/1557779/1/Bello_elife-22964-v2.pdf; https://discovery.ucl.ac.uk/id/eprint/1557779/
Rights: open
Accession Number: edsbas.3A0CCBF2
Database: BASE