Evolution of the Multivesicular Body ESCRT Machinery; Retention Across the Eukaryotic Lineage

Abstract

Lysosomal targeting of ubiquitylated endocytic cargo is mediated in part by the endosomal sorting complex required for transport (ESCRT) complexes, a system conserved between animals and fungi (Opisthokonta). Extensive comparative genomic analysis demonstrates that ESCRT factors are well conserved across the eukaryotic lineage and complexes I, II, III and III-associated are almost completely retained, indicating an early evolutionary origin. The conspicuous exception is ESCRT 0, which functions in recognition of ubiquitylated cargo, and is restricted to the Opisthokonta, suggesting that a distinct mechanism likely operates in the vast majority of eukaryotic organisms. Additional analysis suggests that ESCRT III and ESCRT III-associated components evolved through a concerted model. Functional conservation of the ESCRT system is confirmed by direct study in trypanosomes. Despite extreme sequence divergence, epitope-tagged ESCRT factors TbVps23 and TbVps28 localize to the endosomal pathway, placing the trypanosome multivesicular body (MVB) in juxtaposition to the early endosome and lysosome. Knockdown of TbVps23 partially prevents degradation of an ubiquitylated endocytosed transmembrane domain protein. Therefore, despite the absence of an ESCRT 0 complex, the trypanosome ESCRT/MVB system functions similarly to that of opisthokonts. Thus the ESCRT system is an ancient and well-conserved feature of eukaryotic cells but with key differences between diverse lineages.

Evidence for a Nonendosomal Function of the Saccharomyces cerevisiae ESCRT-III-Like Protein Chm7

“…We name this protein, encoded by yeast ORF YJL049w, Chm7. CHMP7 is found in the genomes of most eukaryotic taxa (Leung et al 2008). This suggests that CHMP7 is also a very ancient component of the ESCRT machinery, which was possibly already present in the "last common eukaryotic ancestor."…”

“…Chm7 is an ancient protein already present in the "last common eukaryotic ancestor" (which did not have a nucleus) (Leung et al 2008). Thus, the Chm7 complex could have a more fundamental function that remains to be elucidated.…”

Multivesicular Bodies Mature from the Trans-Golgi Network/Early Endosome in Arabidopsis

“…Plants also possess ESCRT proteins (Winter and Hauser, 2006;Schellmann and Pimpl, 2009;Shahriari et al, 2011), but there are no clear homologs to the ESCRT-0 complex (Leung et al, 2008), and the exact location of the other complexes is unclear. Nevertheless, several studies with mutated ESCRT proteins point to their presence at least at the LE.…”

A Bioinformatical Approach to Study the Endosomal Sorting Complex Required for Transport (ESCRT) Machinery in Protozoan Parasites: The Entamoeba histolytica Case

“…Among the latter is the ability of eukaryotic cells to incorporate macromolecules, complexes and other cells through endocytosis (de Souza et al, 2009 (Allen et al, 2007;Tse et al, 2004;Yang et al, 2004). Lysosomal targeting of ubiquitinated cargo by ESCRT complexes is conserved in animals and fungi (Leung et al, 2008). Extensive experimental and bioinformatical comparative analysis of genomic data indicate that ESCRT factors are well conserved across the eukaryotic lineage (Williams & Urbé, 2007).…”

“…A common ancestry within the same ESCRT complexes or among them, has been reported for Vps20, Vps32 and Vps60 proteins (sharing a Snf7 domain), and Vps2, Vps24 and Vps46 proteins (sharing a Vps24 domain). All these proteins are highly similar at sequence level and are encoded by multicopy genes, probably due to gene amplification events (Leung et al, 2008). In terms of biological conservation, it seems that several ESCRT components had to be expanded to provide functional redundancy.…”