Journal article
The Yeast Alix Homolog Bro1 Functions as a Ubiquitin Receptor for Protein Sorting into Multivesicular Endosomes
Developmental cell, Vol.25(5), pp.520-533
06/10/2013
DOI: 10.1016/j.devcel.2013.04.007
PMCID: PMC3755756
PMID: 23726974
Abstract
Sorting of ubiquitinated membrane proteins into lumenal vesicles of multivesicular bodies is mediated by the Endosomal Sorting Complex Required for Transport (ESCRT) apparatus and accessory proteins such as Bro1, which recruits the deubiquitinating enzyme Doa4 to remove ubiquitin from cargo. Here we propose that Bro1 works as a receptor for the selective sorting of ubiquitinated cargos. We found synthetic genetic interactions between BRO1 and ESCRT-0, suggesting that Bro1 functions similarly to ESCRT-0. Multiple structural approaches demonstrated that Bro1 binds ubiquitin via the N-terminal trihelical arm of its middle V domain. Mutants of Bro1 that lack the ability to bind Ub were dramatically impaired in their ability to sort Ub-cargo membrane proteins, but only when combined with hypomorphic alleles of ESCRT-0. These data suggest that Bro1 and other Bro1 family members function in parallel with ESCRT-0 to recognize and sort Ub-cargos.
Details
- Title: Subtitle
- The Yeast Alix Homolog Bro1 Functions as a Ubiquitin Receptor for Protein Sorting into Multivesicular Endosomes
- Creators
- Natasha Pashkova - University of IowaLokesh Gakhar - Roy J. and Lucille A. Carver College of MedicineStanley C. Winistorfer - University of IowaAnna B. Sunshine - University of WashingtonMatthew Rich - University of WashingtonMaitreya J. Dunham - University of WashingtonLiping Yu - Roy J. and Lucille A. Carver College of MedicineRobert C. Piper - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Developmental cell, Vol.25(5), pp.520-533
- Publisher
- Elsevier
- DOI
- 10.1016/j.devcel.2013.04.007
- PMID
- 23726974
- PMCID
- PMC3755756
- ISSN
- 1534-5807
- eISSN
- 1878-1551
- Number of pages
- 14
- Grant note
- F30 CA165440 / National Cancer Institute Grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P41 GM103533 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA T32AG000057 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) T32 AG000057 / National Institute on Aging Grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) R01GM058202 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) F30CA165440 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) GM58202 / National Institutes of Health (NIH) Grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 06/10/2013
- Academic Unit
- Molecular Physiology and Biophysics; Biochemistry and Molecular Biology; Medicine Administration; Internal Medicine
- Record Identifier
- 9984297503202771
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