title: Formation of multivesicular endosomes in Dictyostelium.
abstract: Multivesicular endosomes are present in virtually every eucaryotic cell, where they arise by intra-endosomal budding of the limiting endosomal membrane. Some genetic diseases such as Chediak-Higashi syndrome are characterized by enlarged membrane-filled endosomes. The same altered endosomal morphology can be observed in cells exposed to certain drugs, for example U18666A. The mechanisms involved are still poorly characterized, partially because this atypical budding event is particularly difficult to observe in mammalian cells. Taking advantage of the simplicity of the endosomal structure in Dictyostelium discoideum, we could visualize intraendosomal budding at the ultrastructural level. In this model organism, the drug U18666A was shown to stimulate intra-endosomal budding, while an inhibitor of PI 3-kinase activity was found to have no effect on this process. Inactivation of a Dictyostelium gene with similarity to the gene responsible for Chediak-Higashi syndrome did not alter the intra-endosomal budding or the accumulation of intra-endosomal membranes. Thus, although treatment with U18666A and inactivation of the Chediak-Higashi gene cause similar morphological defects in mammalian cells, observations in a different model reveal that their respective modes of action are different.
authors.affiliation: Université de Genève, Centre Médical Universitaire, Département de Physiologie Cellulaire et Métabolisme, 1 rue Michel Servet, 1211 Genève 4, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Marchetti
authors.forename: Valentina
authors.initials: V
authors.lastname: Mercanti
authors.forename: Sophie
authors.initials: S
authors.lastname: Cornillon
authors.forename: Laeticia
authors.initials: L
authors.lastname: Alibaud
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Charette
authors.forename: Pierre
authors.initials: P
authors.lastname: Cosson
mesh_terms: D000736:Androstenes / Q000494:pharmacology; D000818:Animals; D003001:Cloning, Molecular; D004023:Dictyostelium / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism / Q000502:physiology*; D005614:Freeze Fracturing; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009154:Mutation; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D021381:Protein Transport; D013997:Time Factors
chemical_list: D000736:Androstenes; D049452:Green Fluorescent Proteins; C006261:3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one; D019869:Phosphatidylinositol 3-Kinases