ESCRT-dependent cargo sorting at multivesicular endosomes

Abstract

The endosomal sorting complex required for transport (ESCRT) machinery is composed of five multi-subunit protein complexes, which act cooperatively at specialized endosomes to facilitate the movement of specific cargoes from the limiting membrane into vesicles that bud into the endosome lumen. Over the past decade, numerous proteins, lipids, and RNAs have been shown to be incorporated into intralumenal vesicles (ILVs), but the mechanisms by which these unique cargoes are captured are only now becoming better understood. Here, we discuss the potential roles that the ESCRT machinery plays during cargo sorting at multivesicular endosomes (MVEs).

Keywords: Cargo sorting; ESCRT machinery; Intralumenal vesicle; Multivesicular endosome; Ubiquitin.

Figure 1. The early acting ESCRT machinery harbors multiple ubiquitin binding domains

Several components of ESCRT-0, ESCRT-I and ESCRT-II contain domains capable of low affinity association with ubiquitin.

Figure 2. Two speculative models to describe pathways for ESCRT-III spiral filament assembly

In one model (left), a subdomain formed by the early acting ESCRT machinery nucleates ESCRT-III filaments that spiral outward to surround cargoes destined for incorporation into ILVs. In this model, ESCRT-0, ESCRT-I and ESCRT-II must dissociate from the endosomal membrane to avoid engulfment into ILVs. An alternative model (right) suggests that the early acting ESCRT machinery forms a subdomain adjacent to ESCRT-III filaments, which spiral inwards toward a preferred radius of curvature. In this case, cargoes must be transferred between the early and late acting ESCRT complexes.