The cell biology of the endocytic system from an evolutionary perspective

Abstract

Evolutionary cell biology can afford an interdisciplinary comparative view that gives insights into both the functioning of modern cells and the origins of cellular systems, including the endocytic organelles. Here, we explore several recent evolutionary cell biology studies, highlighting investigations into the origin and diversity of endocytic systems in eukaryotes. Beginning with a brief overview of the eukaryote tree of life, we show how understanding the endocytic machinery in a select, but diverse, array of organisms provides insights into endocytic system origins and predicts the likely configuration in the last eukaryotic common ancestor (LECA). Next, we consider three examples in which a comparative approach yielded insight into the function of modern cellular systems. First, using ESCRT-0 as an example, we show how comparative cell biology can discover both lineage-specific novelties (ESCRT-0) as well as previously ignored ancient proteins (Tom1), likely of both evolutionary and functional importance. Second, we highlight the power of comparative cell biology for discovery of previously ignored but potentially ancient complexes (AP5). Finally, using examples from ciliates and trypanosomes, we show that not all organisms possess canonical endocytic pathways, but instead likely evolved lineage-specific mechanisms. Drawing from these case studies, we conclude that a comparative approach is a powerful strategy for advancing knowledge about the general mechanisms and functions of endocytic systems.

Figure 1.

Endocytic proteins as distributed across the eukaryotic supergroups. Some factors, such as the ESCRT-I, -II, -III, and -III-associated proteins, are found in most or all the lineages and thus deduced as being present in the ancestor of eukaryotes (filled blue circle). Other factors, such as ESCRT-0 or the trypanosome-clathrin machinery, are found in a narrowly distributed range of lineages and are thus deduced as arising more recently (open circles). Because the exact relationship of the CCTH and SAR lineages is currently unresolved, these are grouped as a single supergroup. (Blue) Gains of proteins; (red) losses. Although AP5, Tom1-esc, and sortilin all have more complicated distributions, to illustrate ancient factors lost in opisthokonts, only the loss of TBC-rootA is shown. For the full details of the evolutionary history of these proteins, see Herman et al. (2011), Hirst et al. (2011), and Koumandou et al. (2011).

Figure 2.

Endomembrane organelles and vesicle trafficking pathways. The general locations of endocytic factors discussed in detail (ESCRTs, the adaptin 5 complex, and clathrin complexes) are shown on a simplified cartoon of the endomembrane organelles in the eukaryotic cell.

Figure 3.

Localization of components of the ESCRT machinery in trypanosomes. Two components of the ESCRT-I system were localized using ectopic expression of epitope-tagged versions of the relevant proteins. Tsg101/Vps23 (green) and Vps28 (red) are shown, together with the location of the nucleus (N) and kinetoplast (arrowhead), visualized with DAPI (blue). The region of the cell that contains essentially all of the endocytic apparatus is highlighted in the DAPI panel, and is clearly where both Tsg101 and Vps28 are localized. The absence of complete concordance between the two ESCRT factors suggests possible discrete targeting/functional differentiation of late endosome/MVB membranes in trypanosomes. Note that in trypanosomes there is a potential second Tsg101 paralog, which has not so far been investigated. Scale bar, 2 μm. (For more details, see Leung et al. 2008 and Silverman et al. 2013.)