PMID- 25086066 OWN - NLM STAT- MEDLINE DCOM- 20151113 LR - 20211021 IS - 1477-9137 (Electronic) IS - 0021-9533 (Print) IS - 0021-9533 (Linking) VI - 127 IP - Pt 20 DP - 2014 Oct 15 TI - Dictyostelium LvsB has a regulatory role in endosomal vesicle fusion. PG - 4356-67 LID - 10.1242/jcs.138123 [doi] AB - 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 (mu3- 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 mu3- 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. CI - (c) 2014. Published by The Company of Biologists Ltd. FAU - Falkenstein, Kristin AU - Falkenstein K AD - Section of Molecular Cell and Developmental Biology and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA. FAU - De Lozanne, Arturo AU - De Lozanne A AD - 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. LA - eng GR - R01 GM048745/GM/NIGMS NIH HHS/United States GR - R21 AI078136/AI/NIAID NIH HHS/United States GR - GM48745/GM/NIGMS NIH HHS/United States GR - AI078136/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140801 PL - England TA - J Cell Sci JT - Journal of cell science JID - 0052457 RN - 0 (Cytoskeletal Proteins) RN - 0 (LYST protein, human) RN - 0 (Protozoan Proteins) RN - 0 (Vesicular Transport Proteins) RN - 0 (vac A protein, Dictyostelium discoideum) SB - IM MH - Biological Evolution MH - Chediak-Higashi Syndrome/*genetics MH - Cytoskeletal Proteins/metabolism MH - Dictyostelium MH - Endosomes/metabolism MH - Humans MH - Lysosomes/genetics/*metabolism MH - Membrane Fusion/genetics MH - Phagocytosis/genetics MH - Phenotype MH - Protozoan Proteins/genetics/*metabolism MH - Sequence Homology, Amino Acid MH - Vesicular Transport Proteins/genetics/*metabolism PMC - PMC4197084 OTO - NOTNLM OT - Chediak-Higashi syndrome OT - Endosome fusion OT - LvsB OT - Lyst EDAT- 2014/08/03 06:00 MHDA- 2015/11/14 06:00 PMCR- 2015/10/15 CRDT- 2014/08/03 06:00 PHST- 2014/08/03 06:00 [entrez] PHST- 2014/08/03 06:00 [pubmed] PHST- 2015/11/14 06:00 [medline] PHST- 2015/10/15 00:00 [pmc-release] AID - jcs.138123 [pii] AID - 10.1242/jcs.138123 [doi] PST - ppublish SO - J Cell Sci. 2014 Oct 15;127(Pt 20):4356-67. doi: 10.1242/jcs.138123. Epub 2014 Aug 1.