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

• DOI: 10.1101/401190
• Publication Date: 2018-08-27T13:24:22Z
• Authors: Fabrizio Vacca; Stefania Vossio; Vincent Mercier; Dimitri Moreau; Shem Johnson; Jonathan Paz Montoya; Marc Moniatte; Jean Gruenberg
• Keywords: NPC1; Lysosomal storage disease; Secretory Vesicle

ABSTRACT In specialized cell types, lysosome-related organelles support regulated secretory pathways, while in non-specialized cells, lysosomes can undergo fusion with the plasma membrane response to a transient rise cytosolic calcium. Recent evidence also indicates that lysosome secretion be controlled transcriptionally and promote clearance storage diseases. addition, is accumulating low concentrations of cyclodextrins reduce cholesterol phenotype cells animals disease Niemann-Pick type C, via an unknown mechanism. Here, we report cyclodextrin triggers endo/lysosomal content this mechanism responsible for decreased overload C cells. We find endo/lysosome occurs dependent on endosomal calcium channel MCOLN1, as well FYCO1, AP1 adaptor its partner Gadkin. conclude endolysosomes acquire functions elicited by cyclodextrin, pathway decrease