Dumping of MVB cargo (green) into the vacuole (red) fails in mutants (right) that cannot oligomerize ESCRT-I.
MVBs are endosomes with internal vesicles. The vesicles contain membrane proteins bound for fusion with lysosomes or viral particles hoping to escape from the cell. Vesicles bud internally from the endosomal membrane with help from three ESCRT complexes (I, II, and III) that are sequentially recruited from the cytosol to the endosome. Chu et al. found a new component that helps keep this recruitment in proper order.
The helper is a small protein, which the authors call Mvb12, that binds to ESCRT-I and regulates its associations. With Mvb12, most ESCRT-I was found in stable cytoplasmic oligomers (probably trimers). Exactly how Mvb12 stabilizes the oligomers is not clear.
The oligomerization seems to mask ESCRT-I's binding site for ESCRT-II; in the absence of Mvb12, ESCRT-I was instead locked together with ESCRT-II, both in the cytoplasm and on endosomes. Their premature joining resulted in inefficient sorting into MVBs; much of the MVB cargo remained on the endosomal surface.
The authors now want to understand how Mvb12 release is prompted to allow timely ESCRT-II binding. Encountering PI3P and ubiquitinated cargo on the endosome might release Mvb12, resulting in oligomer disassembly and ESCRT-II binding. The final stages of MVB formation, including ESCRT-III recruitment, can then follow. 
