Regulation of yeast ESCRT-III membrane scission activity by the Doa4 ubiquitin hydrolase.

Mol Biol Cell

Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309

Published: March 2017

AI Article Synopsis

  • ESCRT-III is responsible for cutting membranes to form intralumenal vesicles (ILVs) in endosomes, but how this process happens is still unclear.
  • The stability of ESCRT-III complexes and the timing of membrane scission is influenced by the ubiquitin hydrolase Doa4, which delays ILV budding while cargo proteins are modified.
  • Doa4's interaction with the subunit Vps20 of ESCRT-III inhibits the deubiquitination of cargoes, suggesting a mechanism that prevents cargo modification until ESCRT-III assembly is underway.

Article Abstract

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 membrane scission. We show that in , 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 deubiquitination of ILV cargoes is inhibited via 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328624PMC
http://dx.doi.org/10.1091/mbc.E16-11-0761DOI Listing

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