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J Neurosci. 2015 Apr 8;35(14):5772-80. doi: 10.1523/JNEUROSCI.3983-14.2015.

A structural role for the synaptobrevin 2 transmembrane domain in dense-core vesicle fusion pores.

Author information

Department of Neuroscience, University of Wisconsin, Madison, Wisconsin 53705.
Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, California 94158.
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109.
Institut für Physiologie, Universität des Saarlandes, 66424 Homburg, Germany, and.
Department of Neuroscience, University of Wisconsin, Madison, Wisconsin 53705, Howard Hughes Medical Institute, University of Wisconsin, Madison, Wisconsin 53706.
Department of Neuroscience, University of Wisconsin, Madison, Wisconsin 53705,


Ca(2+)-triggered release of neurotransmitters and hormones depends on soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) to drive the fusion of the vesicle and plasma membranes. The formation of the SNARE complex by the vesicle SNARE synaptobrevin 2 (syb2) and the two plasma membrane SNAREs syntaxin (syx) and SNAP-25 draws the two membranes together, but the events that follow membrane juxtaposition, and the ways that SNAREs remodel lipid membranes remain poorly understood. The SNAREs syx and syb2 have transmembrane domains (TMDs) that can exert force directly on the lipid bilayers. The TMD of syx influences fusion pore flux in a manner that suggests it lines the nascent fusion pore through the plasma membrane. The TMD of syb2 traverses the vesicle membrane and is the most likely partner to syx in completing a proteinaceous fusion pore through the vesicle membrane, but the role of this vesicle SNARE in fusion pores has yet to be tested. Here amperometry and conductance measurements were performed to probe the function of the syb2 TMD in fusion pores formed during catecholamine exocytosis in mouse chromaffin cells. Fusion pore flux was sensitive to the size and charge of TMD residues near the N terminus; fusion pore conductance was altered by substitutions at these sites. Unlike syx, the syb2 residues that influence fusion pore permeation fell along two α-helical faces of its TMD, rather than one. These results indicate a role for the syb2 TMD in nascent fusion pores, but in a very different structural arrangement from that of the syx TMD.


calcium-triggered fusion; dense-core vesicle; exocytosis; secretion; synaptobrevin

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