New roles for endosomes: from vesicular carriers to multi-purpose platforms - PubMed (original) (raw)

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New roles for endosomes: from vesicular carriers to multi-purpose platforms

Gwyn W Gould et al. Nat Rev Mol Cell Biol. 2009 Apr.

Abstract

The careful sorting and recycling of membranes and cargo and the intracellular delivery of proteins, toxins and viruses by endocytosis are well-established roles for the endocytic apparatus, which is present in all eukaryotic cells. Recently, it has become clear that endosomes have key roles in such diverse processes as cytokinesis, polarization and migration, in which their functions might be distinct from those classically associated with endosomes. We speculate that endosomes function as multifunctional platforms on which unique sets of molecular machines are assembled to suit different cellular roles.

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Figure 1

Figure 1. Endosome platforms in cytokinesis

For clarity, endosomal trafficking to the midbody and the assembly of the CEP55–ALIX–ESCRT complex (where ALIX is apoptosis-linked gene 2-interacting protein X and ESCRT is endosomal sorting complex required for transport) are drawn on opposite sides of the midbody. In reality, such mechanisms probably exist on both ‘sides’ of the midbody ring. a | During late telophase, RAB11- and RAB35-positive endosomes accumulate in the midbody by interacting with the vesicle-tethering exocyst complex, which is localized to the midbody ring by centriolin (not shown) and perhaps by interacting with BRUCE (see the main text). BRUCE is delivered to the midbody on membrane vesicles, on which it can also function as a diffusion barrier, preventing vesicle movement through the furrow. Collectively, these interactions anchor vesicles in the midbody. b | BRUCE is a ubiquitin ligase through which endosomal cargo might become ubiquitylated. CEP55 recruits ALIX and TSG101, which are components of ESCRTI, into the midbody. ESCRTII and ESCRTIII might also become localized here, perhaps through interactions with ALIX or TSG101, or with ubiquitylated endosomal cargo. These events might occur at the same time as vesicle docking (part a). c | ESCRT proteins form a lattice on endosomal membranes and induce membrane deformation. ESCRT complexes might also facilitate sorting away from midbody-localized endosomes, perhaps removing a ‘fusion brake’. The microtubule-severing protein spastin binds to the ESCRTIII subunit CHMP1B (charged multivesicular body protein 1B). These events (lattice formation and recruitment of spastin) might take place on endosomal surfaces, providing a degree of spatial resolution. In response to a signal, perhaps from an adjacent signalling complex, endosomes (and secretory vesicles) undergo compound fusion. CEP55 in the midbody ring might also function to recruit signalling proteins, such as Aurora B and Polo-like kinase 1 (PLK1), into this region. If spatially and temporally coupled to spastin cleavage of microtubules, this might constitute the basic machinery of abscission.

Figure 2

Figure 2. Endosome platforms in cell migration

The schematic shows a cell that is directing traffic towards circular dorsal ruffles (right) and at the same time disassembles focal adhesions at the rear of the cell (left). RAB5- and dynamin-dependent internalization of cell surface cargo (including Rac) into endosomes is shown (steps 1,2). The endosomes, which are characterized by RAB5, traffic Rac into an endosomal subcompartment that contains the Rac guanine nucleotide-exchange factor TiAM1, resulting in GTP loading, and activation, of Rac (step 3). Vesicles bud off of this compartment and contain activated RAC1 for forward-directed trafficking to the zone of ruffling (step 4). These vesicles might also contain integrin cargo and possibly lipid raft domains. The GTPase ARF6 has been implicated in the trafficking of both rafts and integrins, and hence it is possible that the intracellular endosomal compartment is a focal point for the assembly of an actin-remodelling ‘machine’ that traffics in an ARF6-dependent manner, possibly along microtubules towards the ruffles (step 5). Rafts are known to recycle through caveolae, which contain the protein caveolin 1 (CAV1; step 6). This recycling involves ARF6, suggesting a possible link between these two processes. Focal adhesion disassembly at the rear of the cell might also involve endosome platforms. The pro-migratory receptor ENDO180 (also known as MRC2) traffics between the cell surface and endosomes (step 7). On an appropriate cue, ENDO180 traffic is redirected into endosomes at the rear of the cell near focal adhesions, and serves as a platform for the assembly of Rho–ROCK1–MLC2-derived contractile signals (where MLC2 is myosin light chain 2 and ROCK1 is Rho-associated kinase 1) directly at sites of focal adhesions (steps 8,9).

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