Multi-modal proteomic characterization of lysosomal function and proteostasis in progranulin-deficient neurons.

ABSTRACT:

Background

Progranulin (PGRN) is a lysosomal glycoprotein implicated in various neurodegenerative diseases, including frontotemporal dementia and neuronal ceroid lipofuscinosis. Over 70 mutations discovered in the GRN gene all result in reduced expression of the PGRN protein. Genetic and functional studies point toward a regulatory role for PGRN in lysosome functions. However, the detailed molecular function of PGRN within lysosomes and the impact of PGRN deficiency on lysosomes remain unclear.

Methods

We developed multifaceted proteomic techniques to characterize the dynamic lysosomal biology in living human neurons and fixed mouse brain tissues. Using lysosome proximity labeling and immuno-purification of intact lysosomes, we characterized lysosome compositions and interac

SUBMITTER: Hasan S 

PROVIDER: S-EPMC10655356 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature