title: Retromer-driven membrane tubulation separates endosomal recycling from Rab7/Ypt7-dependent fusion.
abstract: Endosomes are the major protein-sorting hubs of the endocytic pathway. They sort proteins destined for degradation into internal vesicles while in parallel recycling receptors via tubular carriers back to the Golgi. Tubule formation depends on the Rab7/Ypt7-interacting retromer complex, consisting of the sorting nexin dimer (SNX-BAR) and the trimeric cargo selection complex (CSC). Fusion of mature endosomes with the lysosome-like vacuole also requires Rab7/Ypt7. Here we solve a major problem in understanding this dual function of endosomal Rab7/Ypt7, using a fully reconstituted system, including purified, full-length yeast SNX-BAR and CSC, whose overall structure we present. We reveal that the membrane-active SNX-BAR complex displaces Ypt7 from cargo-bound CSC during formation of recycling tubules. This explains how a single Rab can coordinate recycling and fusion on endosomes.
authors.affiliation: Department of Biology/Chemistry, Biochemistry Section, University of Osnabrück, 49076 Osnabrück, Germany.
authors.forename: Latha Kallur
authors.initials: LK
authors.lastname: Purushothaman
authors.affiliation: Department of Biology/Chemistry, Biochemistry Section, University of Osnabrück, 49076 Osnabrück, Germany hearlt@hsph.harvard.edu cu@uos.de.
authors.forename: Henning
authors.initials: H
authors.lastname: Arlt
authors.affiliation: Department of Structural Biochemistry, Max-Planck Institute of Molecular Physiology, 44227 Dortmund, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Kuhlee
authors.affiliation: Department of Structural Biochemistry, Max-Planck Institute of Molecular Physiology, 44227 Dortmund, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Raunser
authors.affiliation: Department of Biology/Chemistry, Biochemistry Section, University of Osnabrück, 49076 Osnabrück, Germany hearlt@hsph.harvard.edu cu@uos.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Ungermann
mesh_terms: D001692:Biological Transport; D011992:Endosomes / Q000378:metabolism* / Q000502:physiology; D006056:Golgi Apparatus / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D058305:Sorting Nexins / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D000090802:rab7 GTP-Binding Proteins
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; D000090802:rab7 GTP-Binding Proteins; C079005:YPT7 protein, S cerevisiae; D020691:rab GTP-Binding Proteins