@article{ef7aa0eb941f45d6899dfd9515ec3f11,
title = "Transcriptional activation of lysosomal exocytosis promotes cellular clearance",
abstract = "Lysosomes are cellular organelles primarily involved in degradation and recycling processes. During lysosomal exocytosis, a Ca 2+-regulated process, lysosomes are docked to the cell surface and fuse with the plasma membrane (PM), emptying their content outside the cell. This process has an important role in secretion and PM repair. Here we show that the transcription factor EB (TFEB) regulates lysosomal exocytosis. TFEB increases the pool of lysosomes in the proximity of the PM and promotes their fusion with PM by raising intracellular Ca 2+ levels through the activation of the lysosomal Ca 2+ channel MCOLN1. Induction of lysosomal exocytosis by TFEB overexpression rescued pathologic storage and restored normal cellular morphology both in vitro and in vivo in lysosomal storage diseases (LSDs). Our data indicate that lysosomal exocytosis may directly modulate cellular clearance and suggest an alternative therapeutic strategy for disorders associated with intracellular storage.",
author = "Medina, \{Diego L.\} and Alessandro Fraldi and Valentina Bouche and Fabio Annunziata and Gelsomina Mansueto and Carmine Spampanato and Claudia Puri and Antonella Pignata and Martina, \{Jose A.\} and Marco Sardiello and Michela Palmieri and Roman Polishchuk and Rosa Puertollano and Andrea Ballabio",
note = "Funding Information: We thank P. Barba, J. Cancino, P. Colella, F. Donaudy, L. Pisapia, and A. Luciani for technical assistance. We thank E. Neufeld, B. Davidson, N. Andrews, C. Tam, and P. De Camilli for helpful discussions. We would like to acknowledge Elena Polishchuk and Anastasia Egorova for help in execution of microscopy experiments as well as Telethon Electron Microscopy Core Facility (IBP, CNR, Naples) and Integrated Microscopy Facility (IGB, CNR, Naples) for EM support. We also thank B. Lelouvier and the NHLBI Light Microscopy Core Facility for their help with the calcium experiments. We also thank G. Diez-Roux, G. Parenti, A. Luini, and A. De Matteis for comments on the manuscript. We acknowledge the support of the Italian Telethon Foundation (D.L.M., A.F., V.B., F.A., G.M., C.S., A.P., and A.B); the European Research Council Advanced Investigator grant number \# 250154 (A.B); the European Commission under the FP7 EUCLYD project (Grant No. HEALTH-2007-A-201678); the Beyond Batten Disease Foundation (M.S and A.B); MPS Society (D.L.M, A.F.and A.B.). J.M. and R.P. are supported by the Intramural Research Program of the NIH, National Heart, Lung, and Blood Institute (NHLBI). In addition, we would like to thank the TIGEM AAV vector core for virus production. ",
year = "2011",
month = sep,
day = "13",
doi = "10.1016/j.devcel.2011.07.016",
language = "English",
volume = "21",
pages = "421--430",
journal = "Developmental cell",
issn = "1534-5807",
number = "3",
}