Lysosomal cholesterol activates mTORC1 via an SLC38A9-Niemann-Pick C1 signaling complex

Science

Volumn 355, Issue 6331, 2017, Pages 1306-1311

  Castellano, Brian M ^a   Thelen, Ashley M ^a   Moldavski, Ofer ^a   Feltes, McKenna ^b   Van Der Welle, Reini E N ^a   Mydock McGrane, Laurel ^b   Jiang, Xuntian ^b   Van Eijkeren, Robert J ^a   Davis, Oliver B ^a   Louie, Sharon M ^a   Perera, Rushika M ^c   Covey, Douglas F ^b   Nomura, Daniel K ^a   Ory, Daniel S ^b   Zoncu, Roberto ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE; CHOLESTEROL; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MEMBRANE PROTEIN; NIEMANN PICK C1 PROTEIN; SLC38A9 PROTEIN; UNCLASSIFIED DRUG; AMINO ACID TRANSPORTER; CARRIER PROTEIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MULTIPROTEIN COMPLEX; NUCLEAR PROTEIN; PICK1 PROTEIN, HUMAN; SLC38A9 PROTEIN, HUMAN; TARGET OF RAPAMYCIN KINASE;

CELLS AND CELL COMPONENTS; GENE; GENETIC ANALYSIS; GROWTH REGULATOR; INHIBITION; PROTEIN;

ARTICLE; CELL GROWTH; CELL SURFACE; HUMAN; LYSOSOME; NUTRIENT; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; ANIMAL; ANTAGONISTS AND INHIBITORS; CHO CELL LINE; CRICETULUS; ENZYME ACTIVATION; FIBROBLAST; GENETICS; HEK293 CELL LINE; METABOLISM; MOUSE; MUTATION; PROTEIN MOTIF; TRANSPORT AT THE CELLULAR LEVEL;

AMINO ACID MOTIFS; AMINO ACID TRANSPORT SYSTEMS; ANIMALS; BIOLOGICAL TRANSPORT; CARRIER PROTEINS; CHO CELLS; CHOLESTEROL; CHOLESTEROL, HDL; CRICETULUS; ENZYME ACTIVATION; FIBROBLASTS; HEK293 CELLS; HUMANS; LYSOSOMES; MICE; MULTIPROTEIN COMPLEXES; MUTATION; NUCLEAR PROTEINS; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES;

EID: 85016302146     PISSN: 00368075     EISSN: 10959203     Source Type: Journal    
DOI: 10.1126/science.aag1417     Document Type: Article

References (30)

1. A. Nohturfft, S. C. Zhang, Annu. Rev. Cell Dev. Biol. 25, 539-566 (2009).
2. P. J. Espenshade, A. L. Hughes, Annu. Rev. Genet. 41, 401-427 (2007).
3. J. L. Goldstein, M. S. Brown, Cell 161, 161-172 (2015).
4. C. C. Dibble, B. D. Manning, Nat. Cell Biol. 15, 555-564 (2013).
5. N. Y. Kalaany, D. J. Mangelsdorf, Annu. Rev. Physiol. 68, 159-191 (2006).
6. H. J. Kwon et al., Cell 137, 1213-1224 (2009).
7. T. Kobayashi et al., Nat. Cell Biol. 1, 113-118 (1999).
8. D. S. Ory, Trends Cardiovasc. Med. 14, 66-72 (2004).
9. E. Kim, P. Goraksha-Hicks, L. Li, T. P. Neufeld, K. L. Guan, Nat. Cell Biol. 10, 935-945 (2008).
10. Y. Sancak et al., Cell 141, 290-303 (2010).
11. Y. Sancak et al., Science 320, 1496-1501 (2008).
12. R. M. Perera, R. Zoncu, Annu. Rev. Cell Dev. Biol. 32, 223-253 (2016).
13. S. Menon et al., Cell 156, 771-785 (2014).
14. J. L. Owen et al., Proc. Natl. Acad. Sci. U.S.A. 109, 16184-16189 (2012).
15. J. L. Yecies et al., Cell Metab. 14, 21-32 (2011).
16. K. Düvel et al., Mol. Cell 39, 171-183 (2010).
17. S. H. Um et al., Nature 431, 200-205 (2004).
18. A. Radhakrishnan, J. L. Goldstein, J. G. McDonald, M. S. Brown, Cell Metab. 8, 512-521 (2008).
19. K. K. Berneis, R. M. Krauss, J. Lipid Res. 43, 1363-1379 (2002).
20. A. R. Tee, B. D. Manning, P. P. Roux, L. C. Cantley, J. Blenis, Curr. Biol. 13, 1259-1268 (2003).
21. R. Zoncu et al., Science 334, 678-683 (2011).
22. L. Bar-Peled, L. D. Schweitzer, R. Zoncu, D. M. Sabatini, Cell 150, 1196-1208 (2012).
23. I. Derler et al., Sci. Signal. 9, ra10 (2016).
24. M. Rebsamen et al., Nature 519, 477-481 (2015).
25. S. Wang et al., Science 347, 188-194 (2015).
26. J. Fantini, F. J. Barrantes, Front. Physiol. 4, 31 (2013).
27. J. L. Goldstein, R. A. DeBose-Boyd, M. S. Brown, Cell 124, 35-46 (2006).
28. E. E. Millard et al., J. Biol. Chem. 280, 28581-28590 (2005).
29. D. Jelinek et al., Hum. Mol. Genet. 20, 312-321 (2011).
30. D. Meyre et al., Nat. Genet. 41, 157-159 (2009).