Open AccessBro1 stimulates Vps4 to promote intralumenal vesicle formation during multivesicular body biogenesis
Author(s) -
Chun-Che Tseng,
Shirley Dean,
Brian A. Davies,
Ishara F. Azmi,
Natalya Pashkova,
Johanna A. Payne,
Jennifer Staffenhagen,
Matt West,
Robert C. Piper,
Greg Odorizzi,
David J. Katzmann
Publication year - 2021
Publication title -
the journal of cell biology/the journal of cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.414
H-Index - 380
eISSN - 1540-8140
pISSN - 0021-9525
DOI - 10.1083/jcb.202102070
Subject(s) - escrt , endosome , biogenesis , microbiology and biotechnology , tsg101 , aaa proteins , biology , transport protein , ubiquitin , vesicle , vacuolar protein sorting , protein targeting , vesicular transport proteins , membrane protein , biochemistry , atpase , membrane , gene , microvesicles , enzyme , microrna , intracellular
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.