Different Niemann-Pick C1 Genotypes Generate Protein Phenotypes that Vary in their Intracellular Processing, Trafficking and Localization.

ABSTRACT: Niemann-Pick Type C (NP-C) is an inherited neurovisceral lysosomal storage disease characterized by a defect in the trafficking of endocytosed cholesterol. In 95% of patients the gene encoding NPC1 is affected. The correlation of the genetic background in NP-C with the clinical phenotype such as, severity and onset of liver dysfunction, ataxia, dystonia and vertical gaze palsy, has not been elucidated at the molecular level. We have designed strategies to investigate the effect of different mutations in the NPC1 gene at the protein and cellular levels. The NPC1 mutants were expressed in mammalian cells and their structural features, maturation pathways and subcellular localization elucidated. Interestingly, three classes of NPC1 mutants could be identified and further characterized. The fi

SUBMITTER: Shammas H 

PROVIDER: S-EPMC6438969 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature