Principles of vesicle trafficking
Membrane vesicles are formed on donor membranes and fuse with specific target membranes. Vesicle formation requires the activities of conserved protein families such as ARF guanine-nucleotide exchange factors (ARF-GEFs) and their substrates, ARF GTPases, as well as specific coat proteins and GTPase-activating proteins (ARF-GAPs) (Fig. 1a). Transport vesicles interact with their target membrane via RAB GTPases and tethering proteins. Subsequent membrane fusion is mediated by the formation of 4-helical trans-SNARE complexes between R-SNAREs (v-SNAREs or VAMPs) on the vesicle and Q-SNAREs or t-SNAREs (syntaxins/Qa-SNAREs and t-SNARE light chains/Qb,Qc-SNAREs or SNAP25/Qb,c-SNAREs) on the target membrane (Fig. 2).
Figure 1 ARF-GEFs and vesicle formation
(a) ARF GDP/GTP cycle. Cytosolic ARF-GDP is recruited to membrane by ARF-GEF mediating GDP-GTP exchange. ARF-GAP stimulated GTP hydrolysis leads to dissociation of ARF-GDP from the membrane.
Figure 2 Membrane fusion through SNARE complex formation
Disassembly of the cis-SNARE complex converts the open form of syntaxin to a closed form (5), which has to be reverted before trans-SNARE complex formation (1).