title: Dictyostelium LvsB has a regulatory role in endosomal vesicle fusion.
abstract: Defects in human lysosomal-trafficking regulator (Lyst) are associated with the lysosomal disorder Chediak-Higashi syndrome. The absence of Lyst results in the formation of enlarged lysosome-related compartments, but the mechanism for how these compartments arise is not well established. Two opposing models have been proposed to explain Lyst function. The fission model describes Lyst as a positive regulator of fission from lysosomal compartments, whereas the fusion model identifies Lyst as a negative regulator of fusion between lysosomal vesicles. Here, we used assays that can distinguish between defects in vesicle fusion versus fission. We compared the phenotype of Dictyostelium discoideum cells defective in LvsB, the ortholog of Lyst, with that of two known fission defect mutants (μ3- and WASH-null mutants). We found that the temporal localization characteristics of the post-lysosomal marker vacuolin, as well as vesicular acidity and the fusion dynamics of LvsB-null cells are distinct from those of both μ3- and WASH-null fission defect mutants. These distinctions are predicted by the fusion defect model and implicate LvsB as a negative regulator of vesicle fusion.
authors.affiliation: Section of Molecular Cell and Developmental Biology and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Falkenstein
authors.affiliation: Section of Molecular Cell and Developmental Biology and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA a.delozanne@utexas.edu.
authors.forename: Arturo
authors.initials: A
authors.lastname: De Lozanne
mesh_terms: D005075:Biological Evolution; D002609:Chediak-Higashi Syndrome / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004023:Dictyostelium; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism*; D008561:Membrane Fusion / Q000235:genetics; D010587:Phagocytosis / Q000235:genetics; D010641:Phenotype; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; C102161:LYST protein, human; D015800:Protozoan Proteins; D033921:Vesicular Transport Proteins; C105803:vac A protein, Dictyostelium discoideum
keywords: Chediak–Higashi syndrome; Endosome fusion; LvsB; Lyst
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