The lipid kinase VPS34 complexes I and II are both activated by unsaturation of substrate and non-substrate lipids, curvature, electrostatics and polyphosphoinositides, which play roles in localisation and cellular function.
Sec1/Munc18 (SM) proteins shield SNARE complexes from NSF/Sec18-mediated disassembly through cooperative binding interactions with SNARE complexes and the universal co-chaperone α-SNAP/Sec17.
Sec17 is shown to have divergent effects on pre-fusion SNARE complex activity, depending on the state of SNARE zippering and HOPS, an SM-tether complex, controls the outcome of Sec17-SNARE engagement.
Vps29 promotes retromer localization in the adult Drosophila brain, engaging Rab7 and TBC1D5, and its loss triggers age-dependent neuronal impairments in endolysosomal trafficking and synaptic transmission.
Whereas in a paradigmatic structure an SM protein chaperone clamps its client SNARE shut, a second structure demonstrates that an SM protein can also hold its SNARE open to promote assembly.
The presynaptic scaffolding protein Bassoon is involved in regulating neurotransmitter release by controlling synaptic vesicle pool size and vesicular protein turnover through increased ubiquitination and Parkin-dependent autophagy.
The tethering complex HOPS employs affinity for each of the 4 SNAREs to catalyze assembly of 3-SNARE intermediates, supporting an immediate burst of membrane fusion triggered by the 4th SNARE.
The endosomal GEF Mon1-Ccz1 binds to Atg8 on autophagosomes, and recruits its substrate, the Rab7-like Ypt7, which then mediates fusion of the autophagosomes with the lysosome.
