title: Β-hexosaminidase over-expression affects lysosomal glycohydrolases expression and glycosphingolipid metabolism in mammalian cells.
abstract: Lysosomes are not only degrading organelles but also involved in other critical cellular processes. In addition, active lysosomal glycohydrolases have been detected in an extra-lysosomal compartment: the presence of glycohydrolases on the plasma membrane (PM) has been widely demonstrated, and a possible role on the modification of the cell surface glycosphingolipids (GSL) participating in the modulation of cell functions such as cell-to-cell interactions and signal transduction pathways has been proposed. On this basis, the coordinated expression of lysosomal glycohydrolases and their translocation to the PM appear to be crucial for many cellular events. In this paper, we report evidence for the existence of a coordinated mechanism regulating the expression/activity of both lysosomal and PM-associated glycohydrolases. We show that the over-expression of the acidic glycohydrolase β-hexosaminidase α-subunit in mouse NIH/3T3 fibroblasts induces the increased expression of the Hex β-subunit necessary to form the active isoenzyme dimers as well as of other glycohydrolases participating in the GSL catabolism, such as β-galactosidase and β-glucocerebrosidase. More interestingly, this regulatory effect was also extended to the PM-associated hydrolases. In addition, transfected cells displayed a rearrangement of the GSL expression pattern that cannot be simply explained by the increased activity of a single enzyme. These observations clearly indicate that the expression level of metabolically related glycohydrolases is regulated in a coordinated manner and this regulation mechanism also involves the PM-associated isoforms.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06123 Perugia, Italy.
authors.forename: Brunella
authors.initials: B
authors.lastname: Tancini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Magini
authors.forename: Barbara
authors.initials: B
authors.lastname: Bortot
authors.forename: Alice
authors.initials: A
authors.lastname: Polchi
authors.forename: Lorena
authors.initials: L
authors.lastname: Urbanelli
authors.forename: Sandro
authors.initials: S
authors.lastname: Sonnino
authors.forename: Giovanni Maria
authors.initials: GM
authors.lastname: Severini
authors.forename: Carla
authors.initials: C
authors.lastname: Emiliani
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000201:enzymology*; D005089:Exocytosis; D005347:Fibroblasts / Q000201:enzymology*; D006026:Glycoside Hydrolases / Q000378:metabolism*; D006028:Glycosphingolipids / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D051379:Mice; D041681:NIH 3T3 Cells; D014162:Transfection; D054820:beta-Hexosaminidase alpha Chain / Q000235:genetics / Q000378:metabolism*
chemical_list: D006028:Glycosphingolipids; D006026:Glycoside Hydrolases; C518253:HEXA protein, human; D054820:beta-Hexosaminidase alpha Chain