The Niemann-Pick C1 Protein Functions in Regulating Lysosome Amine Content

Abstract

Mutations in the lysosome membrane protein Niemann-Pick C1 (NPC1) are known to cause a generalized block in retrograde vesicle-mediated transport from the lysosome, resulting in the hyper-accumulation of multiple lysosomal cargos. As a result, the true substrate of NPC1 is controversial and not fully understood at the current time. An important, yet often overlooked, category of lysosomal cargo includes the vast array of small molecular weight amine-containing molecules that are substrates for ion trapping in the highly acidic organelle lumen. In this dissertation, we provide experimental evidence to support a novel functional role for NPC1 involving the intracellular trafficking of amine-containing molecules.