Fig. 2. AAA proteins involved in membrane fusion. (A) NSF (N-ethylmaleimide-sensitive fusion protein) acts to separate cis SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein proteins) complexes formed as a consequence of membrane fusion. The freed v-SNAREs (blue) are recycled so that they can be incorporated into new transport vesicles and thereby eventually form trans SNARE complexes with t-SNAREs (red) in the target membrane. (B) p97 separates t-SNARE complexes on post-mitotic membranes, allowing subsequent trans SNARE pairing and membrane fusion. Ubiquitinated cofactors may regulate SNARE disassembly by helping to recruit p47–p97. (C,D) Two possible modes of ubiquitin-dependent multivesicular body (MVB) formation. In C, ubiquitinated cargo recruits ESCRT-I, which recruits/activates ESCRT-II and ESCRT-III complexes, forming a domain in the endosome membrane that restricts cargo and selects it for incorporation into internal vesicles (ESCRT-III recruitment is linked to deubiquitination). The ESCRT-III complex is recycled by VPS4. In D, recruited ESCRT-III may act directly during internal vesicle invagination in an analogous way to SNARE-mediated membrane fusion. Again, VPS4 is required for ESCRT-III recycling.

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