[HTML][HTML] Lysosomal processing of progranulin

X Zhou, DH Paushter, T Feng, L Sun… - Molecular …, 2017 - Springer
X Zhou, DH Paushter, T Feng, L Sun, T Reinheckel, F Hu
Molecular neurodegeneration, 2017Springer
Background Mutations resulting in progranulin (PGRN) haploinsufficiency cause
frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP), a
devastating neurodegenerative disease. PGRN is localized to the lysosome and important
for proper lysosome function. However, the metabolism of PGRN in the lysosome is still
unclear. Results Here, we report that PGRN is processed into~ 10 kDa peptides
intracellularly in multiple cell types and tissues and this processing is dependent on …
Background
Mutations resulting in progranulin (PGRN) haploinsufficiency cause frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP), a devastating neurodegenerative disease. PGRN is localized to the lysosome and important for proper lysosome function. However, the metabolism of PGRN in the lysosome is still unclear.
Results
Here, we report that PGRN is processed into ~10 kDa peptides intracellularly in multiple cell types and tissues and this processing is dependent on lysosomal activities. PGRN endocytosed from the extracellular space is also processed in a similar manner. We further demonstrated that multiple cathepsins are involved in PGRN processing and cathepsin L cleaves PGRN in vitro.
Conclusions
Our data support that PGRN is processed in the lysosome through the actions of cathepsins.
Springer