PMID- 32184262
OWN - NLM
STAT- MEDLINE
DCOM- 20210621
LR  - 20220531
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 133
IP  - 8
DP  - 2020 Apr 28
TI  - The ubiquitin hydrolase Doa4 directly binds Snf7 to inhibit recruitment of 
      ESCRT-III remodeling factors in S. cerevisiae.
LID - 10.1242/jcs.241455 [doi]
LID - jcs241455
AB  - The ESCRT-III protein complex executes reverse-topology membrane scission. The 
      scission mechanism is unclear but is linked to remodeling of ESCRT-III complexes 
      at the membrane surface. At endosomes, ESCRT-III mediates the budding of 
      intralumenal vesicles (ILVs). In Saccharomyces cerevisiae, ESCRT-III activity at 
      endosomes is regulated through an unknown mechanism by Doa4, an ubiquitin 
      hydrolase that deubiquitylates transmembrane proteins sorted into ILVs. We report 
      that the non-catalytic N-terminus of Doa4 binds Snf7, the predominant ESCRT-III 
      subunit. Through this interaction, Doa4 overexpression alters Snf7 assembly 
      status and inhibits ILV membrane scission. In vitro, the Doa4 N-terminus inhibits 
      association of Snf7 with Vps2, which functions with Vps24 to arrest Snf7 
      polymerization and remodel Snf7 polymer structure. In vivo, Doa4 overexpression 
      inhibits Snf7 interaction with Vps2 and also with the ATPase Vps4, which is 
      recruited by Vps2 and Vps24 to remodel ESCRT-III complexes by catalyzing subunit 
      turnover. Our data suggest a mechanism by which the deubiquitylation machinery 
      regulates ILV biogenesis by interfering with ESCRT-III remodeling.
CI  - (c) 2020. Published by The Company of Biologists Ltd.
FAU - Buysse, Dalton
AU  - Buysse D
AD  - Department of Molecular, Cellular, and Developmental Biology, University of 
      Colorado, Boulder, CO 80309, USA.
FAU - Pfitzner, Anna-Katharina
AU  - Pfitzner AK
AUID- ORCID: 0000-0001-9952-5525
AD  - Department of Biochemistry, University of Geneva, Geneva CH-1211, Switzerland.
FAU - West, Matt
AU  - West M
AD  - Department of Molecular, Cellular, and Developmental Biology, University of 
      Colorado, Boulder, CO 80309, USA.
FAU - Roux, Aurelien
AU  - Roux A
AUID- ORCID: 0000-0002-6088-0711
AD  - Department of Biochemistry, University of Geneva, Geneva CH-1211, Switzerland.
AD  - Swiss National Centre for Competence in Research Program Chemical Biology, Geneva 
      CH-1211, Switzerland.
FAU - Odorizzi, Greg
AU  - Odorizzi G
AUID- ORCID: 0000-0002-1143-1098
AD  - Department of Molecular, Cellular, and Developmental Biology, University of 
      Colorado, Boulder, CO 80309, USA odorizzi@colorado.edu.
LA  - eng
GR  - 311536/ERC_/European Research Council/International
GR  - R01 GM111335/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200428
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (DID4 protein, S cerevisiae)
RN  - 0 (DOA4 protein, S cerevisiae)
RN  - 0 (Endosomal Sorting Complexes Required for Transport)
RN  - 0 (SNF7 protein, S cerevisiae)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Ubiquitin)
RN  - 0 (VPS4 protein, S cerevisiae)
RN  - EC 3.- (Hydrolases)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.19.12 (Ubiquitin Thiolesterase)
RN  - EC 3.6.1.- (Adenosine Triphosphatases)
SB  - IM
MH  - Adenosine Triphosphatases/genetics/metabolism
MH  - Endopeptidases/*metabolism
MH  - Endosomal Sorting Complexes Required for Transport/genetics/*metabolism
MH  - Endosomes/metabolism
MH  - Hydrolases/metabolism
MH  - Protein Transport
MH  - *Saccharomyces cerevisiae/genetics/metabolism
MH  - Saccharomyces cerevisiae Proteins/genetics/*metabolism
MH  - Ubiquitin/metabolism
MH  - Ubiquitin Thiolesterase/*metabolism
PMC - PMC7197871
OTO - NOTNLM
OT  - ESCRT-III
OT  - Endosome
OT  - Membrane
OT  - Scission
OT  - Ubiquitin
COIS- Competing interestsThe authors declare no competing or financial interests.
EDAT- 2020/03/19 06:00
MHDA- 2021/06/22 06:00
PMCR- 2021/04/28
CRDT- 2020/03/19 06:00
PHST- 2019/11/07 00:00 [received]
PHST- 2020/03/02 00:00 [accepted]
PHST- 2020/03/19 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/03/19 06:00 [entrez]
PHST- 2021/04/28 00:00 [pmc-release]
AID - jcs.241455 [pii]
AID - JCS241455 [pii]
AID - 10.1242/jcs.241455 [doi]
PST - epublish
SO  - J Cell Sci. 2020 Apr 28;133(8):jcs241455. doi: 10.1242/jcs.241455.