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. 2021 Jun 23;220(8):e202102070. doi: 10.1083/jcb.202102070

Figure 10.

Figure 10.

Model of Bro1 “licensing” ESCRT-III membrane remodeling.(A) Bro1 interacts with ESCRTs via interactions between PRR and early ESCRTs, as well as Bro1 domain (BOD) and ESCRT-III. Depicted are two activities of the Bro1 V domain, binding to the Vps4 MIT domain in a manner distinct from ESCRT-III MIM1 and MIM2 elements (curved black arrow), and stimulation of Vps4 ATPase activity (curved green arrow); Ub binding to the V domain potentiates Vps4 stimulation and promotes ILV formation (curved green arrow). These activities contribute to MVB biogenesis and efficient cargo sorting (straight black arrow). (B) When the BOD is deleted, Bro1ΔBOD (via the V domain) improperly activates Vps4 and facilitates ILV formation without efficient cargo sorting. (C) Bro1 without the ability to stimulate the Vps4 (Bro1*, e.g., mutants M4, M8, M9, M10) disrupts MVB cargo sorting and perturbs ILV formation. (D) The absence of BRO1 (bro1Δ) abrogates V domain stimulation of Vps4 as well as Bro1 interactions with early ESCRTs and ESCRT-III; thus, bro1Δ exhibits severe defects in both cargo sorting and ILV formation.