Title |
The lysosomal protein cathepsin L is a progranulin protease
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Published in |
Molecular Neurodegeneration, July 2017
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DOI | 10.1186/s13024-017-0196-6 |
Pubmed ID | |
Authors |
Chris W. Lee, Jeannette N. Stankowski, Jeannie Chew, Casey N. Cook, Ying-Wai Lam, Sandra Almeida, Yari Carlomagno, Kwok-Fai Lau, Mercedes Prudencio, Fen-Biao Gao, Matthew Bogyo, Dennis W. Dickson, Leonard Petrucelli |
Abstract |
Haploinsufficiency of GRN, the gene encoding progranulin (PGRN), causes frontotemporal lobar degeneration (FTLD), the second most common cause of early-onset dementia. Receptor-mediated lysosomal targeting has been shown to regulate brain PGRN levels, and complete deficiency of PGRN is a direct cause of neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. Here we show that the lysosomal cysteine protease cathepsin L (Cat L) can mediate the proteolytic cleavage of intracellular PGRN into poly-granulin and granulin fragments. Further, PGRN and Cat L co-localize in lysosomes of HEK293 cells, iPSC-derived neurons and human cortical neurons from human postmortem tissue. These data identify Cat L as a key intracellular lysosomal PGRN protease, and provides an intriguing new link between lysosomal dysfunction and FTLD. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 25% |
Unknown | 3 | 75% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 50% |
Scientists | 1 | 25% |
Science communicators (journalists, bloggers, editors) | 1 | 25% |
Mendeley readers
Geographical breakdown
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Unknown | 77 | 100% |
Demographic breakdown
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Student > Bachelor | 13 | 17% |
Student > Doctoral Student | 12 | 16% |
Researcher | 12 | 16% |
Student > Master | 7 | 9% |
Other | 8 | 10% |
Unknown | 11 | 14% |
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Chemistry | 3 | 4% |
Other | 5 | 6% |
Unknown | 15 | 19% |