Evolution of the multivesicular body ESCRT machinery: retention across the eukaryotic lineage

Ka Fai Leung, Joel B. Dacks, Mark C. Field

    Research output: Contribution to journalArticle

    163 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)1698-1716
    Number of pages19
    JournalTraffic
    Volume9
    Issue number10
    Early online date14 Jul 2008
    DOIs
    Publication statusPublished - Oct 2008

    Keywords

    • PLASMA-MEMBRANE
    • PROTEIN
    • endocytosis
    • MAXIMUM-LIKELIHOOD
    • SORTING PATHWAY
    • ubiquitin
    • UBIQUITIN
    • vesicle transport
    • multivesicular body
    • MIXED MODELS
    • TRAFFICKING
    • GIARDIA-LAMBLIA
    • trypanosomes
    • ENDOSOME FUNCTION
    • ESCRT
    • TRYPANOSOMA-BRUCEI

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