Transcriptional Activation of Lysosomal Exocytosis Promotes Cellular Clearance

被引：563

作者：

Medina, Diego L. ^{[1
]}

Fraldi, Alessandro ^{[1
]}

Bouche, Valentina ^{[1
]}

Annunziata, Fabio ^{[1
]}

Mansueto, Gelsomina ^{[1
]}

Spampanato, Carmine ^{[1
]}

Puri, Claudia ^{[1
]}

Pignata, Antonella ^{[1
]}

Martina, Jose A. ^{[2
]}

Sardiello, Marco ^{[3
,4
]}

Palmieri, Michela ^{[4
]}

Polishchuk, Roman ^{[1
]}

Puertollano, Rosa ^{[2
]}

Ballabio, Andrea ^{[1
,3
,4
,5
]}

机构：

[1] TIGEM, I-80131 Naples, Italy

[2] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA

[3] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[4] Texas Children Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA

[5] Univ Naples Federico II, Dept Pediat, I-80131 Naples, Italy

来源：

DEVELOPMENTAL CELL | 2011年 / 21卷 / 03期

基金：

欧洲研究理事会;

关键词：

MUCOLIPIDOSIS TYPE-IV; STORAGE DISORDERS; SECRETORY LYSOSOMES; EPITHELIAL-CELLS; MEMBRANE REPAIR; CALCIUM; BIOGENESIS; AUTOPHAGY; IDENTIFICATION; INFLAMMATION;

D O I：

10.1016/j.devcel.2011.07.016

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Lysosomes are cellular organelles primarily involved in degradation and recycling processes. During lysosomal exocytosis, a Ca2+-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 Ca2+ levels through the activation of the lysosomal Ca2+ 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.

引用

页码：421 / 430

页数：10

共 45 条

[1] Regulated secretion of conventional lysosomes [J].