Fig. 5

Global protein turnover and lysosomal degradative function are impaired in progranulin-null human neurons. A Schematic of protein half-life measurements in GRN KO vs. WT i³Neurons using dynamic SILAC proteomics. B Histogram distribution of global protein half-lives in GRN KO (blue) vs. WT (green) i³Neurons. C Volcano plot of protein half-life changes in GRN KO vs. WT i³Neurons. D GO enrichment analysis of biological processes from proteins with significantly slower turnover. E GO enrichment analysis of biological processes from proteins with significantly faster turnover. F KEGG pathways enriched from significantly altered protein half-lives in GRN KO vs. WT i³Neurons. G Schematic of the DQ-BSA Red assay to measure lysosomal degradative function. Extracellular DQ-BSA with self-quenched dye is endocytosed into i³Neurons and trafficked to the lysosome, where it is degraded into smaller protein fragments with isolated fluorophores with fluorescence signals. H Representative fluorescence imaging of DQ-BSA Red assay showing DQ-positive lysosomes in i³Neurons. Scale bar is 10 μm. I Quantification of the fluorescence intensities of the DQ-BSA Red assay in WT vs. GRN KO i³Neurons, normalized to the total number of puncta in two groups