NPC1 trafficking via VPS41-dependent LAMP carriers regulates endosomal cholesterol homeostasis.

ABSTRACT: The Niemann-Pick type 1 and 2 proteins (NPC1 and NPC2) coordinate cholesterol egress from late endosomes-lysosomes (LE/LY). Proper folding, trafficking, and localization of both NPC proteins are essential for normal LE/LY cholesterol handling. Accordingly, mutations in NPC genes cause Niemann-Pick type C (NPC) disease, a progressive neurodegenerative lysosomal cholesterol storage disorder. The routes by which NPC1 reaches the LE/LY compartment in mammalian cells are not fully elucidated. Therefore, to interrogate NPC1 trafficking, we developed genome-engineered HeLa cells expressing endogenous NPC1^mNeon. We demonstrate that endogenous NPC1 localizes to the LE/LY compartment and by using protein proximity-based approaches that NPC1 resides in the same membranes as Vacuolar

SUBMITTER: Ndoj K 

PROVIDER: S-EPMC12772203 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature