Preprint Concept Paper Version 1 Preserved in Portico This version is not peer-reviewed

Roles for the SNAP25 Linker Domain in the Fusion Pore and a Dynamic Plasma Membrane SNARE Acceptor Complex

Version 1 : Received: 25 March 2020 / Approved: 27 March 2020 / Online: 27 March 2020 (02:56:59 CET)

A peer-reviewed article of this Preprint also exists.

Holz, R.W.; Bittner, M.A. Roles for the SNAP25 Linker Domain in the Fusion Pore and a Dynamic Plasma Membrane SNARE “Acceptor” Complex. Journal of General Physiology 2020, 152, doi:10.1085/jgp.202012619. Holz, R.W.; Bittner, M.A. Roles for the SNAP25 Linker Domain in the Fusion Pore and a Dynamic Plasma Membrane SNARE “Acceptor” Complex. Journal of General Physiology 2020, 152, doi:10.1085/jgp.202012619.

Abstract

A recent paper demonstrates the importance of the linker region joining the two SNARE motifs of the neuronal t-SNARE SNAP25 for maintaining rates of secretion with roles for distinct segments in speeding fusion pore expansion (Shaaban et al., 2019, Elife. 8). Remarkably, lipid perturbing agents rescue a palmitoylation-deficient phenotype that includes slow fusion pore expansion, suggesting that protein-protein interactions have a role not only in bringing together the granule or vesicle membrane with the plasma membrane but also in orchestrating protein-lipid interactions leading to the fusion reaction. Furthermore, biochemical investigations demonstrate the importance of the C-terminal domain of the linker in the formation of the plasma membrane t-SNARE acceptor complex for synaptobrevin2 (Jiang, et al., 2019, FASEB J. 33:7985-7994;Shaaban et al., 2019, Elife. 8). This insight, together with biophysical and optical studies from other laboratories (Wang, et al., 2008, Molecular Biology of the Cell. 19:3944-3955; Zhao, et al., 2013, Proc Natl Acad Sci U S A. 110:14249-14254) suggests that the plasma membrane SNARE acceptor complex between SNAP25 and syntaxin and the resulting trans SNARE complex with the v-SNARE synaptobrevin form just milliseconds before fusion.

Keywords

SNAP25; linker; protein lipid interaction; acceptor complex; exocytosis; fusion

Subject

Biology and Life Sciences, Biophysics

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