{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:01:33Z","timestamp":1792094493501,"version":"4.4.0"},"reference-count":51,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,9,14]]},"abstract":"<jats:p>Mutations in the progranulin (PGRN) gene have been linked to two distinct neurodegenerative diseases, frontotemporal lobar degeneration (FTLD) and neuronal ceroid lipofuscinosis (NCL). Accumulating evidence suggests a critical role of PGRN in lysosomes. However, how PGRN is trafficked to lysosomes is still not clear. Here we report a novel pathway for lysosomal delivery of PGRN. We found that prosaposin (PSAP) interacts with PGRN and facilitates its lysosomal targeting in both biosynthetic and endocytic pathways via the cation-independent mannose 6-phosphate receptor and low density lipoprotein receptor-related protein 1. PSAP deficiency in mice leads to severe PGRN trafficking defects and a drastic increase in serum PGRN levels. We further showed that this PSAP pathway is independent of, but complementary to, the previously identified PGRN lysosomal trafficking mediated by sortilin. Collectively, our results provide new understanding on PGRN trafficking and shed light on the molecular mechanisms behind FTLD and NCL caused by PGRN mutations.<\/jats:p>","DOI":"10.1083\/jcb.201502029","type":"journal-article","created":{"date-parts":[[2015,9,14]],"date-time":"2015-09-14T09:34:06Z","timestamp":1442223246000},"page":"991-1002","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":209,"title":["Prosaposin facilitates sortilin-independent lysosomal trafficking of progranulin"],"prefix":"10.1083","volume":"210","author":[{"given":"Xiaolai","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853 1"},{"name":"Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lirong","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853 1"},{"name":"Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853 2"},{"name":"Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Bastos de Oliveira","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853 1"},{"name":"Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Qi","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45229 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus B.","family":"Smolka","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853 1"},{"name":"Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Sun","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenghua","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853 1"},{"name":"Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2015,9,14]]},"reference":[{"key":"2023072308133551600_bib1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1742-2094-4-7","article-title":"Progranulin in frontotemporal lobar degeneration and neuroinflammation","volume":"4","author":"Ahmed","year":"2007","journal-title":"J. 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