{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:08:25Z","timestamp":1791011305162,"version":"4.1.0"},"reference-count":88,"publisher":"The Company of Biologists","issue":"20","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,10,15]]},"abstract":"<jats:p>Niemann-Pick Type C (NP-C) disease, caused by mutations in either human NPC1 (hNPC1) or human NPC2 (hNPC2), is characterized by the accumulation of unesterified cholesterol in late endosomes. Although it is known that the NP-C proteins are targeted to late endosomal\/lysosomal compartments, their delivery mechanisms have not been fully elucidated. To identify mechanisms regulating NP-C protein localization, we used Saccharomyces cerevisiae, which expresses functional homologs of both NP-C proteins \u2013 scNcr1p and scNpc2p. Targeting of scNcr1p to the vacuole was perturbed in AP-3-deficient yeast cells, whereas the delivery of scNpc2p was affected by deficiencies in either AP-3 or GGA. We focused on the role of the AP-3 pathway in the targeting of the mammalian NP-C proteins. We found that, although mouse NPC1 (mNPC1) and hNPC2 co-localize with AP-3 to a similar extent in fibroblasts, hNPC2 preferentially co-localizes with AP-1. Importantly, the targeting of both mammalian NPC1 and NPC2 is dependent on AP-3. Moreover, and consistent with the NP-C proteins playing a role in cholesterol metabolism, AP-3-deficient cells have reduced levels of cholesterol. These results provide information about how the NP-C proteins are targeted to their sites of action and illustrate the possibility that defective sorting of the NP-C proteins along the endocytic route can alter cellular cholesterol.<\/jats:p>","DOI":"10.1242\/jcs.03487","type":"journal-article","created":{"date-parts":[[2007,9,26]],"date-time":"2007-09-26T02:33:37Z","timestamp":1190774017000},"page":"3640-3652","source":"Crossref","is-referenced-by-count":35,"title":["The subcellular localization of the Niemann-Pick Type C proteins depends on the adaptor complex AP-3"],"prefix":"10.1242","volume":"120","author":[{"given":"Adam C.","family":"Berger","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Graduate Program in Biochemistry, Cell, and Developmental Biology, Emory University Graduate Division of Biological and Biomedical Sciences, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Salazar","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie L.","family":"Styers","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Graduate Program in Biochemistry, Cell, and Developmental Biology, Emory University Graduate Division of Biological and Biomedical Sciences, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen A.","family":"Newell-Litwa","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Graduate Program in Biochemistry, Cell, and Developmental Biology, Emory University Graduate Division of Biological and Biomedical Sciences, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Werner","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Maue","sequence":"additional","affiliation":[{"name":"Departments of Physiology and Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita H.","family":"Corbett","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Faundez","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042520070859000_REF1","unstructured":"Adams, A., Gottschling, D. 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