VCIP135 must remove Ub tags for Golgi to reassemble after mitosis.

Chains of ubiquitin (Ub) can mark a protein for degradation by the proteasome. Single Ub tags are commonly used as sorting signals for protein trafficking. Now, on page 973, Wang et al. show that Ub also regulates membrane fusion by cycling onto and off of Golgi membranes before and after mitosis.

The Golgi is dismantled during mitosis into membrane fragments; these are reassembled when division is complete. This fusion event requires the p97 AAA-ATPase and its cofactors, p47 and VCIP135. p97 has various other functions, many of which involve Ub, including extracting Ub-tagged ER proteins from the membrane for transport to the proteasome. Ub is also needed during p97-mediated Golgi reassembly, but the authors find that this requirement has nothing to do with protein degradation.

The proteasome was dispensable for Golgi membrane fusion in vitro, as were chains of Ub, suggesting that unknown substrates are decorated with single Ub units. These individual units had to be removed, however, for p97-mediated fusion to occur, and VCIP135 catalyzes this deubiquitination.

Ub tags were added during fragmentation. They may form a structure that recruits p97 to its substrates (possibly a SNARE or SNARE inhibitor). But the Ub may also inhibit p97 activity (and thus premature reassembly) until mitosis is complete and VCIP135 removes the Ub tag. This suggests that VCIP135 is cell cycle regulated, which has yet to be shown. Next, the authors hope to identify the relevant Ub-tagged Golgi substrates. ▪