PMID- 30889901 OWN - NLM STAT- MEDLINE DCOM- 20190710 LR - 20200225 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 20 IP - 6 DP - 2019 Mar 18 TI - Curcumin Analogue C1 Promotes Hex and Gal Recruitment to the Plasma Membrane via mTORC1-Independent TFEB Activation. LID - 10.3390/ijms20061363 [doi] LID - 1363 AB - The monocarbonyl analogue of curcumin (1E,4E)-1,5-Bis(2-methoxyphenyl)penta-1,4-dien-3-one (C1) has been used as a specific activator of the master gene transcription factor EB (TFEB) to correlate the activation of this nuclear factor with the increased activity of lysosomal glycohydrolases and their recruitment to the cell surface. The presence of active lysosomal glycohydrolases associated with the lipid microdomains has been extensively demonstrated, and their role in glycosphingolipid (GSL) remodeling in both physiological and pathological conditions, such as neurodegenerative disorders, has been suggested. Here, we demonstrate that Jurkat cell stimulation elicits TFEB nuclear translocation and an increase of both the expression of hexosaminidase subunit beta (HEXB), hexosaminidase subunit alpha (HEXA), and galactosidase beta 1 (GLB1) genes, and the recruitment of beta-hexosaminidase (Hex, EC 3.2.1.52) and beta-galactosidase (Gal, EC 3.2.1.23) on lipid microdomains. Treatment of Jurkat cells with the curcumin analogue C1 also resulted in an increase of both lysosomal glycohydrolase activity and their targeting to the cell surface. Similar effects of C1 on lysosomal glycohydrolase expression and their recruitment to lipid microdomains was observed by treating the SH-SY5Y neuroblastoma cell line; the effects of C1 treatment were abolished by TFEB silencing. Together, these results clearly demonstrate the existence of a direct link between TFEB nuclear translocation and the transport of Hex and Gal from lysosomes to the plasma membrane. FAU - Magini, Alessandro AU - Magini A AUID- ORCID: 0000-0002-2750-6226 AD - Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. alessandro.magini@unipg.it. FAU - Polchi, Alice AU - Polchi A AD - Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. alice.polchi@gmail.com. FAU - Di Meo, Danila AU - Di Meo D AD - Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. danila.dimeo@gmail.com. AD - Institute for Molecular Cell Biology, University of Munster, Schlossplatz 5, 48149 Munster, Germany. danila.dimeo@gmail.com. AD - Cells-in-Motion Cluster of Excellence, University of Munster, D-48149 Munster, Germany. danila.dimeo@gmail.com. FAU - Buratta, Sandra AU - Buratta S AD - Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. sandra.buratta@unipg.it. FAU - Chiaradia, Elisabetta AU - Chiaradia E AD - Department of Veterinary Medicine, University of Perugia, Via S. Costanzo 4, 06126 Perugia, Italy. elisabetta.chiaradia@unipg.it. FAU - Germani, Raimondo AU - Germani R AUID- ORCID: 0000-0001-7076-7475 AD - Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. raimondo.germani@unipg.it. FAU - Emiliani, Carla AU - Emiliani C AD - Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. carla.emiliani@unipg.it. FAU - Tancini, Brunella AU - Tancini B AD - Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. brunella.tancini@unipg.it. LA - eng GR - Progetto ISDIS/Fondazione Terzo Pilastro-Internazionale/ PT - Journal Article DEP - 20190318 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors) RN - 0 (Lipid Bilayers) RN - 0 (Phytohemagglutinins) RN - 0 (TFEB protein, human) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) RN - EC 3.2.1.- (Hexosaminidases) RN - EC 3.2.1.23 (beta-Galactosidase) RN - IT942ZTH98 (Curcumin) SB - IM MH - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*metabolism MH - Cell Membrane/drug effects/*metabolism MH - Cell Nucleus/drug effects/metabolism MH - Curcumin/*analogs & derivatives/*pharmacology MH - Exocytosis/drug effects MH - Hexosaminidases/*metabolism MH - Humans MH - Jurkat Cells MH - Lipid Bilayers/metabolism MH - Mechanistic Target of Rapamycin Complex 1/*metabolism MH - Membrane Microdomains/drug effects/metabolism MH - Phytohemagglutinins/pharmacology MH - Protein Transport/drug effects MH - beta-Galactosidase/*metabolism PMC - PMC6471159 OTO - NOTNLM OT - TFEB OT - curcumin OT - curcumin analogue C1 OT - lysosomal glycohydrolases OT - plasma membrane-associated glycohydrolases COIS- The authors declare no conflict of interest. EDAT- 2019/03/21 06:00 MHDA- 2019/07/11 06:00 PMCR- 2019/03/01 CRDT- 2019/03/21 06:00 PHST- 2019/02/21 00:00 [received] PHST- 2019/03/11 00:00 [revised] PHST- 2019/03/15 00:00 [accepted] PHST- 2019/03/21 06:00 [entrez] PHST- 2019/03/21 06:00 [pubmed] PHST- 2019/07/11 06:00 [medline] PHST- 2019/03/01 00:00 [pmc-release] AID - ijms20061363 [pii] AID - ijms-20-01363 [pii] AID - 10.3390/ijms20061363 [doi] PST - epublish SO - Int J Mol Sci. 2019 Mar 18;20(6):1363. doi: 10.3390/ijms20061363.