Format

Send to

Choose Destination
See comment in PubMed Commons below
Nat Struct Mol Biol. 2016 Jan;23(1):67-73. doi: 10.1038/nsmb.3141. Epub 2015 Dec 14.

Exocytotic fusion pores are composed of both lipids and proteins.

Author information

1
Department of Neuroscience, University of Wisconsin-Madison, Madison, Wisconsin, USA.
2
Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, Wisconsin, USA.
3
Department of Pharmacology, University of Cambridge, Cambridge, UK.
4
Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Abstract

During exocytosis, fusion pores form the first aqueous connection that allows escape of neurotransmitters and hormones from secretory vesicles. Although it is well established that SNARE proteins catalyze fusion, the structure and composition of fusion pores remain unknown. Here, we exploited the rigid framework and defined size of nanodiscs to interrogate the properties of reconstituted fusion pores, using the neurotransmitter glutamate as a content-mixing marker. Efficient Ca(2+)-stimulated bilayer fusion, and glutamate release, occurred with approximately two molecules of mouse synaptobrevin 2 reconstituted into ∼6-nm nanodiscs. The transmembrane domains of SNARE proteins assumed distinct roles in lipid mixing versus content release and were exposed to polar solvent during fusion. Additionally, tryptophan substitutions at specific positions in these transmembrane domains decreased glutamate flux. Together, these findings indicate that the fusion pore is a hybrid structure composed of both lipids and proteins.

Comment in

PMID:
26656855
PMCID:
PMC4756907
DOI:
10.1038/nsmb.3141
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center