title: Antagonistic control of lysosomal fusion by Rab14 and the Lyst-related protein LvsB.
abstract: While loss of the protein Lyst causes abnormal lysosomes in patients with Chediak-Higashi syndrome, the contribution of Lyst to lysosome biology is not known. Previously we found that the Dictyostelium ortholog of Lyst, LvsB, is a cytosolic protein that associates with lysosomes and post-lysosomes to prevent their inappropriate fusion. Here we provide three lines of evidence that indicate that LvsB contributes to lysosome function by antagonizing the function of DdRab14, a protein that promotes homotypic fusion among lysosomes. (1) Instead of restricting DdRab14 to lysosomes, cells that lack LvsB expand DdRab14 localization to include post-lysosomes. (2) Expression of activated DdRab14 phenocopies the loss of LvsB, causing inappropriate heterotypic fusion between lysosomes and post-lysosomes and their subsequent enlargement. (3) Conversely, expression of inactivated DdRab14 suppresses the phenotype of LvsB null cells and restores their lysosomal size and segregation from post-lysosomes. Our data suggest a scenario where LvsB binds to late lysosomes and promotes the inactivation of DdRab14. This inactivation allows the lysosomes to mature into post-lysosomes for eventual secretion. We propose that human Lyst may function similarly to regulate Rab-dependent fusion of lysosomal compartments.
authors: Section of Molecular Cell & Developmental Biology and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
authors: Elena
authors: E
authors: Kypri
authors: Kristin
authors: K
authors: Falkenstein
authors: Arturo
authors: A
authors: De Lozanne
mesh_terms: D001692:Biological Transport; D004023:Dictyostelium / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; C102161:LYST protein, human; D015800:Protozoan Proteins; D033921:Vesicular Transport Proteins; C503870:vacuolin-1; D049452:Green Fluorescent Proteins; C553411:Rab14 protein, human; D020691:rab GTP-Binding Proteins
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