Cyclodextrin triggers MCOLN1-dependent endo-lysosome secretion in Niemann-Pick type C cells

Autor: Jonathan Paz Montoya, Stefania Vossio, Cameron C. Scott, Dimitri Moreau, Fabrizio Vacca, Shem Johnson, Jean Gruenberg, Vincent Mercier, Marc Moniatte
Rok vydání: 2019
Předmět:
0301 basic medicine
niemann-pick disease
disease type-c
030204 cardiovascular system & hematology
cholesterol transfer
Biochemistry
Transient Receptor Potential Channels
0302 clinical medicine
Endocrinology
Tumor Cells
Cultured
Research Articles
Chemistry
plasma-membrane
Niemann-Pick Disease
Type C
cellular cholesterol
phospholipids/trafficking
Cell biology
medicine.anatomical_structure
endosomes
cholesterol/trafficking
Sterol binding
exocytosis
Cholesterol storage
secretory lysosomes
bis(monoacylglycero)phosphate
Endosome
QD415-436
Exocytosis
03 medical and health sciences
trafficking
Lysosome
medicine
Humans
endocytosis
Secretion
phospholipids
Cyclodextrins
quantitation
Calcium channel
cholesterol
Cell Biology
sterol binding
030104 developmental biology
Microscopy
Fluorescence
transport
identification
lysobisphosphatidic acid
NPC1
npc1
protein
HeLa Cells
Zdroj: Journal of Lipid Research, Vol 60, Iss 4, Pp 832-843 (2019)
ISSN: 0022-2275
DOI: 10.1194/jlr.m089979
Popis: In specialized cell types, lysosome-related organelles support regulated secretory pathways, whereas in nonspecialized cells, lysosomes can undergo fusion with the plasma membrane in response to a transient rise in cytosolic calcium. Recent evidence also indicates that lysosome secretion can be controlled transcriptionally and promote clearance in lysosome storage diseases. In addition, evidence is also accumulating that low concentrations of cyclodextrins reduce the cholesterol-storage phenotype in cells and animals with the cholesterol storage disease Niemann-Pick type C, via an unknown mechanism. Here, we report that cyclodextrin triggers the secretion of the endo/lysosomal content in nonspecialized cells and that this mechanism is responsible for the decreased cholesterol overload in Niemann-Pick type C cells. We also find that the secretion of the endo/lysosome content occurs via a mechanism dependent on the endosomal calcium channel mucolipin-1, as well as FYCO1, the AP1 adaptor, and its partner Gadkin. We conclude that endo-lysosomes in nonspecialized cells can acquire secretory functions elicited by cyclodextrin and that this pathway is responsible for the decrease in cholesterol storage in Niemann-Pick C cells.
Databáze: OpenAIRE
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