Multivesicular bodies in the enigmatic amoeboflagellateBreviata anathemaand the evolution of ESCRT 0

Abstract

Endosomal sorting complexes required for transport (ESCRTs) are heteromeric protein complexes required for multivesicular body (MVB) morphogenesis. ESCRTs I, II, III and III-associated are ubiquitous in eukaryotes and presumably ancient in origin. ESCRT 0 recruits cargo to the MVB and appears to be opisthokont-specific, bringing into question aspects of the current model of ESCRT mechanism. One caveat to the restricted distribution of ESCRT 0 was the previous limited availability of amoebozoan genomes, the supergroup closest to opisthokonts. Here, we significantly expand the sampling of ESCRTs in Amoebozoa. Our electron micrographic and bioinformatics evidence confirm the presence of MVBs in the amoeboflagellate Breviata anathema. Searches of genomic databases of amoebozoans confirm the ubiquitous nature of ESCRTs I–III-associated and the restriction of ESCRT 0 to opisthokonts. Recently, an alternate ESCRT 0 complex, centering on Tom1 proteins, has been proposed. We determine the distribution of Tom1 family proteins across eukaryotes and show that the Tom1, Tom1L1 and Tom1L2 proteins are a vertebrate-specific expansion of the single Tom1 family ancestor, which has indeed been identified in at least one member of each of the major eukaryotic supergroups. This implies a more widely conserved and ancient role for the Tom1 family in endocytosis than previously suspected.

TOM1 is a PI5P effector involved in the regulation of endosomal maturation

“…It has been proposed that TOM1 and Hrs could play parallel roles in clathrin recruitment and sorting of ubiquitylated cargoes on early endosomal membranes, for their subsequent delivery to the lysosomes. Recent phylogenetic analysis shows that TOM1 family proteins form an ancestral ESCRT-0 complex in the amoeboflagellate Breviate anathema (Herman et al, 2011), as well as in Dictyostelium discoideum (Blanc et al, 2009). The authors demonstrated that in Dictyostelium, DdTOM1 interacts with Esp15, a clathrin adaptor protein involved in EGFR internalization (Benmerah et al, 1998) and degradation by the ESCRT complex (Roxrud et al, 2008).…”

The Roles of ESCRT Proteins in Healthy Cells and in Disease

“…However D. discoideum contains instead a minimal, possibly ancestral ESCRT-0 in which DdTom1 interacts with ubiquitin, clathrin and the ESCRT-1 protein Tsg101 (Blanc et al, 2009). MVBs were also recently identified in the basal amoebozoan Breviata anathema, strengthening the conclusion that the ESCRTs' are a common feature of this supergroup (Herman et al, 2011). In mammals and plants several VpsE genes such as Vps37, Vps4, Vps32, Mvb12 and Bro1 have undergone gene duplications.…”

A Unique N-Terminal Sequence in the Carnation Italian ringspot virus p36 Replicase-Associated Protein Interacts with the Host Cell ESCRT-I Component Vps23

“…Presently, our understanding of ESCRT in plants is relatively poor, and thus, working models based on studies of ESCRT in yeasts and mammals are often employed to infer the mechanisms of ESCRT assembly and function in plants. While this approach has generally proven to be valid because of the overall conserved nature of ESCRT function among evolutionarily diverse organisms, particularly during MVB biogenesis (35,61,62), there are also several features of ESCRT in plants that are distinct, including the ability of TOL proteins to compensate for the lack of ESCRT-0 proteins in terms of ubiquitinated cargo recognition and sorting (16,17). Thus, understanding how different tombusviruses appropriate the plant ESCRT machinery, apparently through different forms of molecular mimicry, as discussed below, not only gives important insight into how tombusviruses manipulate membranes to facilitate their replication but may also provide valuable clues to previously unexplored aspects of normal ESCRT assembly and function in plants.…”

“…Interestingly, while the ESCRT machinery and its interaction network are relatively well conserved and have similar cellular functions in plants compared to yeasts and mammals (14,15), some key differences exist, which are not well understood. For example, homologs of mammalian and yeast ESCRT-0 do not exist in plants (16), and instead, recent work has identified the TOL family of proteins to be involved in early recognition of ubiquitinated cargo and their sorting to MVBs (17). However, the relationship between cargo recognition by TOL proteins and subsequent ESCRT recruitment and assembly has yet to be investigated.…”