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. 2022 Aug;44(8):e2100276.
doi: 10.1002/bies.202100276. Epub 2022 Jun 30.

Bro1 family proteins harmonize cargo sorting with vesicle formation

Chun-Che Tseng  1   2 , Robert C Piper  3 , David J Katzmann  1   2
Affiliations

Bro1 family proteins harmonize cargo sorting with vesicle formation

Chun-Che Tseng et al. Bioessays. 2022 Aug.

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.

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Figures

Figure 1.
Figure 1.
Bro1 V domain interacts with MIT domain of Vps4 via an unknown surface which is independent of MIM1/2. The MIT domain is a single bundle of three alpha-helices (α1, α2, α3). MIM2 interacts with the MIT via the groove between α1 and α3, while MIM1 interacts via the groove between α2 and α3.
Figure 2
Figure 2
Proposed model for Bro1-regulated Vps4-driven ESCRT-III co-polymer remodeling. The ESCRT-III co-polymer contains four features. During ESCRT-III assembly, Snf7 forms the spiral core/backbone (Feature 1), while the Vps24/Vps2 complex binds to the spiral core laterally (Feature 2). Subsequently Bro1 and Vps4 are recruited to drive remodeling (Feature 3 & 4). In remodeling scenario C, Vps4 and Bro1 are omitted for better visualization of ESCRT-III polymer twisting. The neon green arrow indicates Bro1 stimulation of Vps4 ATPase activity.
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