Johnson N, West M, Odorizzi G

ESCRT-III executes membrane scission during the budding of intralumenal vesicles (ILVs) at endosomes. The scission mechanism is unknown but appears to be linked to the cycle of assembly and disassembly of ESCRT-III complexes at membranes. Regulating this cycle is, therefore, expected to be important for determining the timing of ESCRT-III-mediated ...

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membrane scission. We show in Saccharomyces cerevisiae that ESCRT-III complexes are stabilized and ILV membrane scission is delayed by Doa4, which is the ubiquitin hydrolase that deubiquitinates transmembrane proteins sorted as cargoes into ILVs. These results suggest a mechanism to delay ILV budding while cargoes undergo deubiquitination. We further show that the deubiquitination of ILV cargoes is inhibited through Doa4 binding to Vps20, which is the subunit of ESCRT-III that initiates assembly of the complex. Current models suggest that ESCRT-III complexes surround ubiquitinated cargoes to trap them at the site of ILV budding while the cargoes undergo deubiquitination. Thus, our results also propose a mechanism to prevent the onset of ILV cargo deubiquitination at the initiation of ESCRT-III complex assembly.

Date: Jan. 05, 2017

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