Endosomal sorting complex required for transport (ESCRT) proteins are involved in the formation of intraluminal vesicles (ILVs) at multivesicular bodies (MVBs). Teis and colleagues now reveal a role for the ESCRT-associated AAA-ATPase Vps4 in ILV budding (J. Cell Biol. http://doi.org/r8j; 2014).

ESCRT-III proteins wrap around the necks of forming ILVs to promote membrane scission. The ESCRT-III complex is then disassembled and recycled by Vps4, which interacts with the ESCRT-III proteins Vps2, Did2, Vps20, Vps24 and Snf7. The authors expressed Vps4-interaction-deficient ESCRT mutants in yeast, and found that mutations in Vps2 and Snf7 reduced Vps4 association with the ESCRT-III complex and blocked complex disassembly.

Surprisingly, the Vps2 and Snf7 mutants also blocked cargo sorting into the vacuole lumen. In addition, ILVs in Vps2- or Snf7-mutant yeast were larger but formed less frequently than their wild-type counterparts. These observations point to a potential role for Vps4 in ILV generation. The authors propose that Vps4 remodels the ESCRT-III complex to promote membrane deformation, membrane scission and ILV biogenesis. Future experiments aimed at understanding the precise role for Vps4 in these processes, and whether it is required for other ESCRT-III-driven scission events, will provide further support for these intriguing observations.