title: Occurrence of an anomalous endocytic compartment in fibroblasts from Sandhoff disease patients.
abstract: Sandhoff disease (SD) is a lysosomal storage disorder due to mutations in the gene encoding for the beta-subunit of beta-hexosaminidase, that result in beta-hexosaminidase A (alphabeta) and beta-hexosaminidase B (betabeta) deficiency. This leads to the storage of GM2 ganglioside in endosomes and lysosomes, which ends in a progressive neurodegeneration. Currently, very little is known about the biochemical pathways leading from GM2 ganglioside accumulation to pathogenesis. Defects in transport and sorting by the endosomal-lysosomal system have been described for several lysosomal storage disorders. Here, we have investigated the endosomal-lysosomal compartment in fibroblasts from SD patients and observed that both late endosomes and lysosomes, but not early endosomes, have a higher density in comparison with normal fibroblasts. Moreover, Sandhoff fibroblasts have an intracellular distribution of terminal endocytic organelles that differs from the characteristic perinuclear punctate pattern observed in normal fibroblasts and endocytic vesicles also appear larger. These findings reveal the occurrence of an alteration in the terminal endocytic organelles of Sandhoff fibroblasts, suggesting an involvement of this compartment in the disruption of cell metabolic and signalling pathways and in the onset of the pathological state.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, via del Giochetto, 06126 Perugia, Italy.
authors.forename: Brunella
authors.initials: B
authors.lastname: Tancini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Magini
authors.forename: Loredana
authors.initials: L
authors.lastname: Latterini
authors.forename: Lorena
authors.initials: L
authors.lastname: Urbanelli
authors.forename: Virginia
authors.initials: V
authors.lastname: Ciccarone
authors.forename: Fausto
authors.initials: F
authors.lastname: Elisei
authors.forename: Carla
authors.initials: C
authors.lastname: Emiliani
mesh_terms: D002478:Cells, Cultured; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism / Q000648:ultrastructure*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure*; D005455:Fluorescent Antibody Technique; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D012497:Sandhoff Disease / Q000473:pathology*; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics / Q000378:metabolism
chemical_list: D001619:beta-N-Acetylhexosaminidases