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Review
. 2015 Sep;72(18):3441-3455.
doi: 10.1007/s00018-015-1935-x. Epub 2015 May 29.

Biogenesis of endosome-derived transport carriers

Richard J Chi #  1 , Megan S Harrison #  1 , Christopher G Burd  1
Affiliations
Review

Biogenesis of endosome-derived transport carriers

Richard J Chi et al. Cell Mol Life Sci. 2015 Sep.

Abstract

Sorting of macromolecules within the endosomal system is vital for physiological control of nutrient homeostasis, cell motility, and proteostasis. Trafficking routes that export macromolecules from the endosome via vesicle and tubule transport carriers constitute plasma membrane recycling and retrograde endosome-to-Golgi pathways. Proteins of the sorting nexin family have been discovered to function at nearly every step of endosomal transport carrier biogenesis and it is becoming increasingly clear that they form the core machineries of cargo-specific transport pathways that are closely integrated with cellular physiology. Here, we summarize recent progress in elucidating the pathways that mediate the biogenesis of endosome-derived transport carriers.

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Figures

Fig. 1
Fig. 1
Sorting nexin mediated endosome export pathways. As an early, RAB5 GTPase-positive, endosome matures into a RAB7-GTPase-positive endosome, integral membrane proteins and lipids are exported from it via tubules and vesicles, collectively referred to here as ‘endosome-derived transport carriers’ (ETCs). Whereas cargo is sorted into the tubular domain of the endosome for export, the vacuolar domain of the endosome, containing solutes and intra-lumenal vesicles (ILVs) produced by the multi-vesicular body (MVB) sorting pathway, retains material and ultimately fuses with the lysosome where its contents are degraded via the lysosomal degradation pathway. Distinct requirements for three different sorting nexins, SNX27, SNX17 (and its paralog, SNX31), and SNX4, distinguish three export pathways from the early/sorting endosome that ferry cargo to the plasma membrane or the recycling endosome. At least two distinct export pathways operate on more mature endosomes, defined by requirements for the SNX-BAR proteins, SNX1, SNX2, SNX5, and SNX6, or the PX-only sorting nexin, SNX3. These pathways mediate retrograde trafficking of cargo from the endosome to the trans Golgi network (TGN). Where indicated, the retromer sorting device associates with the sorting nexin and contributes to cargo packaging
Fig. 2
Fig. 2
Key features of sorting nexins that mediate export from the endosome. All sorting nexins contain an evolutionarily conserved Phox-homology (PX) domain that recognizes phosphatidylinositol 3-phosphate. a, b Members of the SNX-BAR sub-family of sorting nexins also contain a Bin-Amphiphysin-Rvs (BAR) dimerization domain that displays a curved surface and oligomerizes to coat the membrane of an endosome-derived transport carrier. Subsets of SNX-BARs (colored boxes) have been shown to homo- or heterodimerize. c Model of tubular ETC formation by SNX-BARs. SNX-BAR protomers coat both the vacuolar and tubular domains of the endosome and oligomerize to coat the tubular ETCs. Restricted oligomerization of SNX-BAR protomers, and dependence on other factors such as retromer, define distinct export pathways. d Other evolutionarily conserved SNX proteins implicated in endosome export. Members of the PX-only subfamily are comprised of a single PX domain. So far, SNX3 (and its yeast homolog, ySnx3) are the only members of this sub-family to be implicated in cargo export. Members of the SNX-FERM sub-family contain a C-terminal FERM (band4.1/ezrin/radixin/moesin) domain, which is a protein interaction module that is used for cargo recognition
Fig. 3
Fig. 3
Modes of ETC fission. Depicted are three types of fission events proposed to elicit fission of tubular endosome-derived transport carriers from the mother endosome. a Tensile force produced by coordinated action of F-actin and microtubule-dependent motors. Whereas long range movement of the endosome is mediated by microtubule-dependent motors, such as dynein and kinesins, filamentous actin restricts the motility of endosomes by ‘caging’ or tethering the endosome [121]. Localized increase in microtubule-dependent motor traction and corresponding increase in tensile force relative to the tethered vacuolar domain leads to ETC fission. Local endosome-associated actin dynamics, generated by ARP2/3 and the WASH complex, might also propel the ETC away from the mother endosome to drive fission. b ETC fission occurs at sites where the ETC is contacted by a tubule of the endoplasmic reticulum (ER), however, the role of the ER contact sites in ETC fission has yet to be elucidated. c In yeast, ETC fission is mediated by the dynamin-related protein, Vps1. The SNX-BAR protein, Mvp1, is proposed to facilitate oligomerization of Vps1 on the ETC membrane by constricting the diameter of the tubule, thereby promoting fission. Models are not drawn to scale
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