Journal article
Bro1 stimulates Vps4 to promote intralumenal vesicle formation during multivesicular body biogenesis
The Journal of cell biology, Vol.220(8), e202102070
08/02/2021
DOI: 10.1083/jcb.202102070
PMCID: PMC8240856
PMID: 34160559
Abstract
Endosomal sorting complexes required for transport (ESCRT-0, -I, -II, -III) execute cargo sorting and intralumenal vesicle (ILV) formation during conversion of endosomes to multivesicular bodies (MVBs). The AAA-ATPase Vps4 regulates the ESCRT-III polymer to facilitate membrane remodeling and ILV scission during MVB biogenesis. Here, we show that the conserved V domain of ESCRT-associated protein Bro1 (the yeast homologue of mammalian proteins ALIX and HD-PTP) directly stimulates Vps4. This activity is required for MVB cargo sorting. Furthermore, the Bro1 V domain alone supports Vps4/ESCRT-driven ILV formation in vivo without efficient MVB cargo sorting. These results reveal a novel activity of the V domains of Bro1 homologues in licensing ESCRT-III-dependent ILV formation and suggest a role in coordinating cargo sorting with membrane remodeling during MVB sorting. Moreover, ubiquitin binding enhances V domain stimulation of Vps4 to promote ILV formation via the Bro1-Vps4-ESCRT-III axis, uncovering a novel role for ubiquitin during MVB biogenesis in addition to facilitating cargo recognition.
Details
- Title: Subtitle
- Bro1 stimulates Vps4 to promote intralumenal vesicle formation during multivesicular body biogenesis
- Creators
- Chun-Che Tseng - Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55901 USAShirley Dean - Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55901 USABrian A. Davies - Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55901 USAIshara F. Azmi - Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55901 USANatalya Pashkova - University of Iowa, Molecular Physiology and BiophysicsJohanna A. Payne - Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55901 USAJennifer Staffenhagen - Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55901 USAMatt West - Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USARobert C. Piper - University of Iowa, Molecular Physiology and BiophysicsGreg Odorizzi - Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USADavid J. Katzmann - Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55901 USA
- Resource Type
- Journal article
- Publication Details
- The Journal of cell biology, Vol.220(8), e202102070
- DOI
- 10.1083/jcb.202102070
- PMID
- 34160559
- PMCID
- PMC8240856
- NLM abbreviation
- J Cell Biol
- ISSN
- 0021-9525
- eISSN
- 1540-8140
- Publisher
- Rockefeller Univ Press
- Number of pages
- 24
- Grant note
- DOI: 10.13039/100000871, name: Mayo Clinic; DOI: 10.13039/100000871, name: Mayo Clinic; DOI: 10.13039/100000871, name: Mayo Clinic; DOI: 10.13039/100000002, name: National Institutes of Health, award: R01 GM116826, R01 GM065505, R01 GM58202; DOI: 10.13039/100002069, name: Fraternal Order of Eagles; DOI: 10.13039/100000001, name: National Science Foundation, award: DGE-NSF-01-02; DOI: 10.13039/100000871, name: Mayo Clinic; DOI: 10.13039/100000871, name: Mayo Clinic
- Language
- English
- Date published
- 08/02/2021
- Academic Unit
- Molecular Physiology and Biophysics; Medicine Administration; Internal Medicine
- Record Identifier
- 9984297612102771
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