title: The enlarged lysosomes in beige j cells result from decreased lysosome fission and not increased lysosome fusion.
abstract: Chediak-Higashi syndrome is an autosomal recessive disorder that affects vesicle morphology. The Chs1/Lyst protein is a member of the BEige And CHediak family of proteins. The absence of Chs1/Lyst gives rise to enlarged lysosomes. Lysosome size is regulated by a balance between vesicle fusion and fission and can be reversibly altered by acidifying the cytoplasm using Acetate Ringer's or by incubating with the drug vacuolin-1. We took advantage of these procedures to determine rates of lysosome fusion and fission in the presence or absence of Chs1/Lyst. Here, we show by microscopy, flow cytometry and in vitro fusion that the absence of the Chs1/Lyst protein does not increase the rate of lysosome fusion. Rather, our data indicate that loss of this protein decreases the rate of lysosome fission. We further show that overexpression of the Chs1/Lyst protein gives rise to a faster rate of lysosome fission. These results indicate that Chs1/Lyst regulates lysosome size by affecting fission.
authors: Department of Pathology, School of Medicine, University of Utah, Salt Lake City, UT 84132, USA.
authors: Nina
authors: N
authors: Durchfort
authors: Shane
authors: S
authors: Verhoef
authors: Michael B
authors: MB
authors: Vaughn
authors: Rishna
authors: R
authors: Shrestha
authors: Dieter
authors: D
authors: Adam
authors: Jerry
authors: J
authors: Kaplan
authors: Diane McVey
authors: DM
authors: Ward
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002609:Chediak-Higashi Syndrome / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005434:Flow Cytometry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; D047908:Intracellular Signaling Peptides and Proteins; C102161:LYST protein, human; C491133:Lyst protein, mouse; D011506:Proteins; D033921:Vesicular Transport Proteins; C503870:vacuolin-1