More intralumenal vesicles (red) break away from the endosome membrane in control cells (left) than in cells that overexpress a domain of Bro1 (right).

More intralumenal vesicles (red) break away from the endosome membrane in control cells (left) than in cells that overexpress a domain of Bro1 (right).

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The protein Bro1 lives up to its name, Wemmer et al. show. Like a big brother, Bro1 protects a protein complex that helps pinch off vesicles.

The ESCRT-III complex serves as a pair of molecular scissors that cuts cell membranes, helping to separate dividing cells and enabling viruses such as HIV to bud from the cell surface. The complex also helps endosomes fashion intralumenal vesicles (ILVs), which hold worn-out membrane proteins scheduled for destruction in lysosomes. ESCRT-III snips the nascent vesicles from the endosome membrane. How ESCRT-III promotes membrane scission and how cells manage its activity remain unclear.

Previous work has shown that the ATPase Vps4 breaks up the ESCRT-III complex. Wemmer et al. found that Bro1, which latches onto the Snf7 subunit of ESCRT-III, stands up to Vps4. In yeast cells and in vitro, Bro1's attachment to Snf7 boosted the complex's stability. And ESCRT-III complexes containing a mutant version of Snf7 that rebuffs Bro1 were prone to falling apart. ILVs often remained attached to the endosome membrane in cells expressing extra amounts of Bro1, which might indicate that Vps4's disassembly of the ESCRT-III complex helps snip off the vesicles.

Cells are continually assembling and disassembling ESCRT-III, and Bro1 might allow the subunits to remain together long enough to perform their task. How Bro1 shields ESCRT-III isn't known, but the team suggests that the protein prevents Vps4 from reaching a vulnerable site on the complex. Still uncertain is what keeps Bro1 under control.

Wemmer
M.
et al
.
2011
.
J. Cell Biol.
.