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Updated: Feb 24, 2026
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Modified Yeast-Two-Hybrid System to Identify Proteins Interacting with the Growth Factor Progranulin
Published on: January 17, 2012
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Lysosomal processing of progranulin.
Xiaolai Zhou1, Daniel H Paushter1, Tuancheng Feng1
1Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, 345 Weill Hall, Ithaca, NY, 14853, USA.
Molecular Neurodegeneration
|August 25, 2017
Summary
Progranulin (PGRN) is processed into smaller peptides within lysosomes, a process dependent on cathepsins. This finding clarifies PGRN metabolism and its role in lysosomal function and neurodegenerative diseases like FTLD-TDP.
Area of Science:
- Cell Biology
- Neuroscience
- Biochemistry
Background:
- Mutations in progranulin (PGRN) cause frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP).
- PGRN is crucial for lysosome function, but its lysosomal metabolism remains poorly understood.
- FTLD-TDP is a severe neurodegenerative disease linked to PGRN deficiency.
Purpose of the Study:
- To elucidate the intracellular processing and metabolism of progranulin (PGRN) within lysosomes.
- To investigate the role of lysosomal enzymes in PGRN degradation.
- To understand the mechanism of PGRN processing in relation to lysosomal function.
Main Methods:
- Investigated PGRN processing in various cell types and tissues.
- Assessed the dependence of PGRN processing on lysosomal activity.
- Examined the role of cathepsins in PGRN degradation using in vitro assays.
- Studied extracellularly endocytosed PGRN processing.
Main Results:
- Progranulin (PGRN) is processed into approximately 10 kDa peptides intracellularly.
- PGRN processing is dependent on lysosomal activity and occurs for both intracellular and endocytosed PGRN.
- Multiple cathepsins, including cathepsin L, are involved in PGRN processing.
Conclusions:
- Progranulin (PGRN) undergoes lysosomal processing mediated by cathepsins.
- This clarifies a key aspect of PGRN metabolism relevant to lysosomal function.
- Findings provide insights into the molecular mechanisms underlying PGRN-related neurodegenerative disorders.
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