{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:45:30Z","timestamp":1767919530820,"version":"3.49.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,12,15]],"date-time":"2015-12-15T00:00:00Z","timestamp":1450137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:p>Niemann\u2013Pick type C (NPC) disease is an inherited lysosomal storage disorder, characterized by severe neurodegeneration. It is mostly produced by mutations in the <jats:italic>NPC1<\/jats:italic> gene, encoding for a protein of the late endosomes\/lysosomes membrane, involved in cholesterol metabolism. However, the specific role of this protein in NPC disease still remains unknown. We aimed to identify Npc1\u2010binding proteins in order to define new putative NPC1 lysosomal functions. By affinity chromatography using an Npc1 peptide (amino acids 1032\u20131066 of loop I), as bait, we fished 31 lysosomal proteins subsequently identified by LC\u2010MS\/MS. Most of them were involved in proteolysis and lipid catabolism and included the protease cathepsin D. Cathepsin D and NPC1 interaction was validated by immunoprecipitation and the functional relevance of this interaction was studied. We found that fibroblasts from NPC patients with low levels of NPC1 protein have high amounts of procathepsin D but reduced quantities of the mature protein, thus showing a diminished cathepsin D activity. The increase of NPC1 protein levels in NPC cells by treatment with the proteasome inhibitor bortezomib, induced an elevation of cathepsin D activity. All these results suggest a new lysosomal function of NPC1 as a regulator of cathepsin D processing and activity.<\/jats:p>","DOI":"10.1002\/pmic.201500110","type":"journal-article","created":{"date-parts":[[2015,10,28]],"date-time":"2015-10-28T06:29:14Z","timestamp":1446013754000},"page":"150-158","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Identification of lysosomal Npc1\u2010binding proteins: Cathepsin D activity is regulated by NPC1"],"prefix":"10.1002","volume":"16","author":[{"given":"Judit","family":"Mac\u00edas\u2010Vidal","sequence":"first","affiliation":[{"name":"Secci\u00f3 d'Errors Cong\u00e8nits del Metabolisme (IBC) Servei de Bioqu\u00edmica i Gen\u00e8tica Molecular Hospital Cl\u00ednic  Barcelona Spain"},{"name":"CIBER de Enfermedades Raras (CIBERER), Madrid, Spain"},{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Guerrero\u2010Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Immunology and Neurosciences University of Barcelona  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josep Maria","family":"Estanyol","sequence":"additional","affiliation":[{"name":"Proteomic Unit Centres Cient\u00edfics i Tecnol\u00f2gics University of Barcelona  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Aguado","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Raras (CIBERER), Madrid, Spain"},{"name":"Laboratory of Cellular Biology Centro de Investigaci\u00f3n Pr\u00edncipe Felipe  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erwin","family":"Knecht","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Raras (CIBERER), Madrid, Spain"},{"name":"Laboratory of Cellular Biology Centro de Investigaci\u00f3n Pr\u00edncipe Felipe  Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Josep","family":"Coll","sequence":"additional","affiliation":[{"name":"Secci\u00f3 d'Errors Cong\u00e8nits del Metabolisme (IBC) Servei de Bioqu\u00edmica i Gen\u00e8tica Molecular Hospital Cl\u00ednic  Barcelona Spain"},{"name":"CIBER de Enfermedades Raras (CIBERER), Madrid, Spain"},{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oriol","family":"Bachs","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Department of Cell Biology, Immunology and Neurosciences University of Barcelona  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,12,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.03.012"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-014-9794-4"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4439(94)90001-9"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)45483-X"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302588200"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e04-05-0432"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.037622"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.10.042"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1110439108"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201004142"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12046"},{"key":"e_1_2_8_13_1","first-page":"14","article-title":"The Niemann\u2010Pick C1 and caveolin\u20101 proteins interact to modulate efflux of low density lipoprotein\u2010derived cholesterol from late endocytic compartments","volume":"3","author":"Jelinek D.","year":"2014","journal-title":"J. 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