Intracellular Vesicle Fusion Requires a Membrane-Destabilizing Peptide Located at the Juxtamembrane Region of the v-SNARE

Rathore, Shailendra S.; Liu, Yinghui; Yu, Haijia; Wan, Chun; Lee, MyeongSeon; Yin, Qian; Stowell, Michael H.B.; Shen, Jingshi

Membrane-destabilizing peptides in viral fusion and homotypic ER fusion are usually short segments embedded in the surface of lipid bilayers (Chernomordik and Kozlov, 2003; Earp et al., 2005; Liu et al., 2012) . VAMP2/synaptobrevin, a v-SNARE involved in synaptic exocytosis (Martin et al., 2013; Söllner et al., 1993) , possesses a conserved juxtamembrane motif linking the force-generating SNARE motif to the transmembrane domain ( Figure 1A ; Bowen and Brunger, 2006; Brewer et al., 2011) . Buried in the outer leaflet of the membrane bilayer, the juxtamembrane motif contains hydrophobic residues that insert into the nonpolar phase of the lipid bilayer as well as basic residues localized to the polar phase of the membrane ( Figure 1B ; Bowen and Brunger, 2006; Brewer et al., 2011; Ellena et al., 2009; Kweon et al., 2003) . The juxtamembrane motif is critical for exocytosis in vivo (Borisovska et al.,2012; DeMill et al., 2014; Williams et al., 2009 ), but its role in the membrane fusion reaction has remained unclear.