TFEB activation promotes the recruitment of lysosomal glycohydrolases β-hexosaminidase and β-galactosidase to the plasma membrane

Abstract

Lysosomes are membrane-enclosed organelles containing acid hydrolases. They mediate a variety of physiological processes, such as cellular clearance, lipid homeostasis, energy metabolism and pathogen defence. Lysosomes can secrete their content through a process called lysosome exocytosis in which lysosomes fuse with the plasma membrane realising their content into the extracellular milieu. Lysosomal exocytosis is not only responsible for the secretion of lysosomal enzymes, but it also has a crucial role in the plasma membrane repair. Recently, it has been demonstrated that lysosome response to the physiologic signals is regulated by the transcription factor EB (TFEB). In particular, lysosomal secretion is transcriptionally regulated by TFEB which induces both the docking and fusion of lysosomes with the plasma membrane. In this work we demonstrated that TFEB nuclear translocation is accompanied by an increase of mature glycohydrolases β-hexosaminidase and β-galactosidase on cell surface. This evidence contributes to elucidate an unknown TFEB biological function leading the lysosomal glycohydrolases on plasma membrane.

Keywords: 3GalNAcβ1,4-(NeuAcα2,3)-Galβ1,4Glc-ceramide; 4-methylumbelliferyl-N-acetyl-β-d-glucosaminide; 4-methylumbelliferyl-N-acetyl-β-d-glucosaminide-6-sulphate; 4-methylumbelliferyl-β-d-galactopyranoside; GM1; GM2; GM3; GSLs; Gal; Galβ1,3GalNAcβ1,4-(NeuAcα2,3)-Galβ1,4Glc-ceramide; Hex; Lipid microdomain glycohydrolases; Lysosome exocytosis; MUG; MUGS; MUGal; NeuAcα2,3Galβ1,4Glc-ceramide; Plasma membrane glycohydrolases; TFEB; flot-2; flotillin-2; glycosphingolipids; transcription factor EB; β-galactosidase; β-hexosaminidase.