{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:47:32Z","timestamp":1791978452546,"version":"4.4.0"},"reference-count":26,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2018,5,10]],"date-time":"2018-05-10T00:00:00Z","timestamp":1525910400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,5,10]],"date-time":"2018-05-10T00:00:00Z","timestamp":1525910400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,5,10]],"date-time":"2018-05-10T00:00:00Z","timestamp":1525910400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Nitrogen-containing-bisphosphonates (N-BPs) are a class of drugs widely prescribed to treat osteoporosis and other bone-related diseases. Although previous studies have established that N-BPs function by inhibiting the mevalonate pathway in osteoclasts, the mechanism by which N-BPs enter the cytosol from the extracellular space to reach their molecular target is not understood. Here, we implemented a CRISPRi-mediated genome-wide screen and identified SLC37A3 (solute carrier family 37 member A3) as a gene required for the action of N-BPs in mammalian cells. We observed that SLC37A3 forms a complex with ATRAID (all-trans retinoic acid-induced differentiation factor), a previously identified genetic target of N-BPs. SLC37A3 and ATRAID localize to lysosomes and are required for releasing N-BP molecules that have trafficked to lysosomes through fluid-phase endocytosis into the cytosol. Our results elucidate the route by which N-BPs are delivered to their molecular target, addressing a key aspect of the mechanism of action of N-BPs that may have significant clinical relevance.<\/jats:p>","DOI":"10.7554\/elife.36620","type":"journal-article","created":{"date-parts":[[2018,5,10]],"date-time":"2018-05-10T08:00:30Z","timestamp":1525939230000},"source":"Crossref","is-referenced-by-count":57,"title":["Identification of a transporter complex responsible for the cytosolic entry of nitrogen-containing bisphosphonates"],"prefix":"10.7554","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3213-4583","authenticated-orcid":true,"given":"Zhou","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States"},{"name":"Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren 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