Fig. 5: LysoIP TMT-MS reveals loss of key lysosomal proteins in progranulin-deficient mouse and patient-derived fibroblasts.

A Diagram of 3xHA-tagged TMEM192 used for LysoIP. B Experimental design for LysoIP experiments. C Representative western blot of LysoIP experiment demonstrating specific isolation of lysosomes. Gene ontology of MEF (D) and HDF (E) LysoIP-derived proteins demonstrating enrichment of proteins under the KEGG term ‘lysosome’. Volcano plots of LysoIP isolated lysosomal proteomes from Grn+/− MEFs (n = 6 Grn+/+, n = 6 Grn+/−) (F) and GRN+/− HDFs (n = 3 GRN+/+, n = 6 GRN+/−) (G). H GRN+/− vs GRN+/+ fold changes of whole-cell lysate proteins correlate with fold changes in LysoIP-derived proteins (p = 1.16 × 10−50; simple linear regression). I LysoIP-derived proteins are significantly altered in mouse (n = 6 Grn+/+, n = 6 Grn+/−) and human (n = 3 GRN+/+, n = 6 GRN+/−) progranulin haploinsufficient cell types (*q < 0.05 Two-stage step-up Benjamini, Krieger, and Yekutieli Test). All error bars represent stardard error of the mean.