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Bro1 family proteins harmonize cargo sorting with vesicle formation
Journal article   Open access   Peer reviewed

Bro1 family proteins harmonize cargo sorting with vesicle formation

Chun‐Che Tseng, Robert C. Piper and David J. Katzmann
BioEssays, Vol.44(8), pp.e2100276-n/a
08/2022
DOI: 10.1002/bies.202100276
PMCID: PMC9575758
PMID: 35770783
url
https://www.ncbi.nlm.nih.gov/pmc/articles/9575758View
Open Access

Abstract

The Endosomal Sorting Complexes Required for Transport (ESCRTs) drive membrane remodeling in a variety of cellular processes that include the formation of endosomal intralumenal vesicles (ILVs) during multivesicular body (MVB) biogenesis. During MVB sorting, ESCRTs recognize ubiquitin (Ub) attached to membrane protein cargo and execute ILV formation by controlling the activities of ESCRT‐III polymers regulated by the AAA‐ATPase Vps4. Exactly how these events are coordinated to ensure proper cargo loading into ILVs remains unclear. Here we discuss recent work documenting the ability of Bro1, an ESCRT‐associated Ub‐binding protein, to coordinate ESCRT‐III and Vps4‐dependent ILV biogenesis with upstream events such as cargo recognition. Model of Bro1‐mediated stimulation of Vps4 and intralumenal vesicle (ILV) formation. Bro1 V domain binds and stimulates Vps4 to drive ILV formation, and regulation of this stimulation is required for coordinating cargo sorting. Ubiquitin binding to the V domain can further enhance this mode of stimulation. These ideas build upon previous understandings of Bro1 interactions (ESCRT‐III, Ubiquitin, YPxL, ESCRT‐I, DUbs, and Ub ligase) and outcomes (cargo recognition). BOD, Bro1 domain; DUbs, deubiquitinases; PRR, proline rich domain; ILV, intralumenal vesicle; Ub, ubiquitin; YPxL, amino acids tryptophan, proline, [x], leucine.

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