Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 57,294 bioRxiv papers from 263,837 authors.
Identification and characterization of a transporter complex responsible for the cytosolic entry of nitrogen-containing bisphosphonates
Lauren E Surface,
Chong Yon Park,
Max A Horlbeck,
Gregory A Wyant,
Timothy R Peterson,
David M Sabatini,
Jonathan S Weissman
Posted 27 Mar 2018
bioRxiv DOI: 10.1101/289835
Posted 27 Mar 2018
Nitrogen-containing-bisphosphonates (N-BPs) are 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. 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.
- Downloaded 301 times
- Download rankings, all-time:
- Site-wide: 29,589 out of 57,294
- In biochemistry: 726 out of 1,635
- Year to date:
- Site-wide: 41,456 out of 57,294
- Since beginning of last month:
- Site-wide: 47,028 out of 57,294
Downloads over time
Distribution of downloads per paper, site-wide
- Top preprints of 2018
- Paper search
- Author leaderboards
- Overall metrics
- The API
- Email newsletter
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!