L. interrogans utilizes endocytic recycling and vesicular transport systems for transcytosis across endothelial or epithelial barrier in blood vessels or renal tubules, which contributes to spreading and transmission of leptospirosis.
A novel microscopy-based assay shows that dendritic cells encountering pathogenic stimuli form increased complexes of specific SNARE proteins, driving release of large amounts of inflammatory cytokines.
Rigorous assays of membrane fusion show that a distinct tethering step is required for lumenal compartment mixing in a manner that extends beyond simply increasing the amount of total trans-SNARE complex.
Biophysical analyses indicate that Munc18-1, Munc13-1, synaptotagmin-1 and complexin-1 maintain assembled trans-SNARE complexes in the presence of NSF-alphaSNAP, suggesting that they form part of the primed state of synaptic vesicles.
Building on previous work (Diao et al., 2012), we show that the mechanism by which complexin suppresses spontaneous fusion is distinct from the mechanism by which it synchronizes Ca2+-triggered fusion.
Biophysical and functional data strongly support the notion that Munc18-1 acts as a template to assemble the neuronal SNARE complex, and that inhibition of this activity underlies diverse forms of regulation of neurotransmitter release.