{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:23:15Z","timestamp":1791328995006,"version":"4.3.1"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1993,10,1]]},"abstract":"<jats:p>B lymphocytes from patients with I-cell disease (ICD) maintain normal cellular levels of lysosomal enzymes despite a deficiency of the enzyme UDP-N-acetylglucosamine: lysosomal enzyme N-acetylglucosamine-1-phosphotransferase. We find that an ICD B lymphoblastoid cell line targets about 45% of the lysosomal protease cathepsin D to dense lysosomes. This targeting occurs in the absence of detectable mannose 6-phosphate residues on the cathepsin D and is not observed in ICD fibroblasts. The secretory protein pepsinogen, which is closely related to cathepsin D in both amino acid sequence and three-dimensional structure, is mostly excluded from dense lysosomes, indicating that the lymphoblast targeting pathway is specific. Carbohydrate residues are not required for lysosomal targeting, since a non-glycosylated mutant cathepsin D is sorted with comparable efficiency to the wild type protein. Analysis of a number of cathepsin D\/pepsinogen chimeric proteins indicates that an extensive polypeptide determinant in the cathepsin D carboxyl lobe can confer efficient lysosomal sorting when introduced into the pepsinogen sequence. This determinant overlaps but is not identical to the recognition marker for phosphotransferase. These results indicate that a specific protein recognition event underlies Man-6-P-independent lysosomal sorting in ICD lymphoblasts.<\/jats:p>","DOI":"10.1083\/jcb.123.1.99","type":"journal-article","created":{"date-parts":[[2004,5,15]],"date-time":"2004-05-15T00:22:22Z","timestamp":1084580542000},"page":"99-108","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":114,"title":["Mannose 6-phosphate-independent targeting of lysosomal enzymes in I-cell disease B lymphoblasts."],"prefix":"10.1083","volume":"123","author":[{"given":"J N","family":"Glickman","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Kornfeld","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1993,10,1]]},"container-title":["The Journal of cell biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/123\/1\/99\/1474625\/99.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/123\/1\/99\/1474625\/99.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T04:29:37Z","timestamp":1690000177000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jcb\/article\/123\/1\/99\/14768\/Mannose-6-phosphate-independent-targeting-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,10,1]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1993,10,1]]}},"URL":"https:\/\/doi.org\/10.1083\/jcb.123.1.99","relation":{},"ISSN":["0021-9525","1540-8140"],"issn-type":[{"value":"0021-9525","type":"print"},{"value":"1540-8140","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,10,1]]}}}