title: Binding to any ESCRT can mediate ubiquitin-independent cargo sorting.
abstract: The ESCRT (endosomal sorting complex required for transport) machinery is known to sort ubiquitinated transmembrane proteins into vesicles that bud into the lumen of multivesicular bodies (MVBs). Although the ESCRTs themselves are ubiquitinated they are excluded from the intraluminal vesicles and recycle back to the cytoplasm for further rounds of sorting. To obtain insights into the rules that distinguish ESCRT machinery from cargo we analyzed the trafficking of artificial ESCRT-like protein fusions. These studies showed that lowering ESCRT-binding affinity converts a protein from behaving like ESCRT machinery into cargo of the MVB pathway, highlighting the close relationship between machinery and the cargoes they sort. Furthermore, our findings give insights into the targeting of soluble proteins into the MVB pathway and show that binding to any of the ESCRTs can mediate ubiquitin-independent MVB sorting.
authors.affiliation: Center for Cell and Genome Science and Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT, 84112, USA.
authors.forename: Shrawan Kumar
authors.initials: SK
authors.lastname: Mageswaran
authors.forename: Megan Gorringe
authors.initials: MG
authors.lastname: Dixon
authors.forename: Matt
authors.initials: M
authors.lastname: Curtiss
authors.forename: James P
authors.initials: JP
authors.lastname: Keener
authors.forename: Markus
authors.initials: M
authors.lastname: Babst
mesh_terms: D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D057146:Multivesicular Bodies / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin
keywords: ESCRT; Multivesicular bodies; soluble MVB cargo; ubiquitin-independent cargo sorting