Abstract
In addition to being the terminal degradative compartment of the cell’s endocytic and autophagic pathways, the lysosome is a multifunctional signalling hub integrating the cell’s response to nutrient status and growth factor/hormone signalling. The cytosolic surface of the limiting membrane of the lysosome is the site of activation of the multiprotein complex mammalian target of rapamycin complex 1 (mTORC1), which phosphorylates numerous cell growth-related substrates, including transcription factor EB (TFEB). Under conditions in which mTORC1 is inhibited including starvation, TFEB becomes dephosphorylated and translocates to the nucleus where it functions as a master regulator of lysosome biogenesis. The signalling role of lysosomes is not limited to this pathway. They act as an intracellular Ca2+ store, which can release Ca2+ into the cytosol for both local effects on membrane fusion and pleiotropic effects within the cell. The relationship and crosstalk between the lysosomal and endoplasmic reticulum (ER) Ca2+ stores play a role in shaping intracellular Ca2+ signalling. Lysosomes also perform other signalling functions, which are discussed. Current views of the lysosomal compartment recognize its dynamic nature. It includes endolysosomes, autolysosome and storage lysosomes that are constantly engaged in fusion/fission events and lysosome regeneration. How signalling is affected by individual lysosomal organelles being at different stages of these processes and/or at different sites within the cell is poorly understood, but is discussed.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Allison R, Edgar JR, Pearson G, Rizo T, Newton T, Gunther S, Berner F, Hague J, Connell JW, Winkler J, Lippincott-Schwartz J, Beetz C, Winner B, Reid E (2017) Defects in ER-endosome contacts impact lysosome function in hereditary spastic paraplegia. J Cell Biol 216(5):1337–1355. https://doi.org/10.1083/jcb.201609033
Alonso V, Friedman PA (2013) Minireview: ubiquitination-regulated G protein-coupled receptor signaling and trafficking. Mol Endocrinol 27(4):558–572. https://doi.org/10.1210/me.2012-1404 me.2012-1404 [pii]
Antonioli M, Di Rienzo M, Piacentini M, Fimia GM (2016) Emerging mechanisms in initiating and terminating autophagy. Trends Biochem Sci. https://doi.org/10.1016/j.tibs.2016.09.008
Bar-Peled L, Schweitzer LD, Zoncu R, Sabatini DM (2012) Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1. Cell 150(6):1196–1208. https://doi.org/10.1016/j.cell.2012.07.032
Bar-Peled L, Chantranupong L, Cherniack AD, Chen WW, Ottina KA, Grabiner BC, Spear ED, Carter SL, Meyerson M, Sabatini DM (2013) A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science 340(6136):1100–1106. https://doi.org/10.1126/science.1232044
Bento CF, Renna M, Ghislat G, Puri C, Ashkenazi A, Vicinanza M, Menzies FM, Rubinsztein DC (2016) Mammalian autophagy: how does it work? Annu Rev Biochem 85:685–713. https://doi.org/10.1146/annurev-biochem-060815-014556
Bowman SL, Shiwarski DJ, Puthenveedu MA (2016) Distinct G protein-coupled receptor recycling pathways allow spatial control of downstream G protein signaling. J Cell Biol 214(7):797–806. https://doi.org/10.1083/jcb.201512068
Bright NA, Reaves BJ, Mullock BM, Luzio JP (1997) Dense core lysosomes can fuse with late endosomes and are re-formed from the resultant hybrid organelles. J Cell Sci 110(Pt 17):2027–2040
Bright NA, Gratian MJ, Luzio JP (2005) Endocytic delivery to lysosomes mediated by concurrent fusion and kissing events in living cells. Curr Biol 15(4):360–365. https://doi.org/10.1016/j.cub.2005.01.049 S0960982205001053 [pii]
Bright NA, Davis LJ, Luzio JP (2016) Endolysosomes are the principal intracellular sites of acid hydrolase activity. Curr Biol 26(17):2233–2245. https://doi.org/10.1016/j.cub.2016.06.046 S0960-9822(16)30687-X [pii]
Butor C, Griffiths G, Aronson NN Jr, Varki A (1995) Co-localization of hydrolytic enzymes with widely disparate pH optima: implications for the regulation of lysosomal pH. J Cell Sci 108(Pt 6):2213–2219
Cao Q, Zhong XZ, Zou Y, Murrell-Lagnado R, Zhu MX, Dong XP (2015) Calcium release through P2X4 activates calmodulin to promote endolysosomal membrane fusion. J Cell Biol 209(6):879–894. https://doi.org/10.1083/jcb.201409071
Capel RA, Bolton EL, Lin WK, Aston D, Wang Y, Liu W, Wang X, Burton RA, Bloor-Young D, Shade KT, Ruas M, Parrington J, Churchill GC, Lei M, Galione A, Terrar DA (2015) Two-pore channels (TPC2 s) and nicotinic acid adenine dinucleotide phosphate (NAADP) at lysosomal-sarcoplasmic reticular junctions contribute to acute and chronic beta-adrenoceptor signaling in the heart. J Biol Chem 290(50):30087–30098. https://doi.org/10.1074/jbc.M115.684076
Carmona-Gutierrez D, Hughes AL, Madeo F, Ruckenstuhl C (2016) The crucial impact of lysosomes in aging and longevity. Ageing Res Rev 32:2–12. https://doi.org/10.1016/j.arr.2016.04.009
Carnell M, Zech T, Calaminus SD, Ura S, Hagedorn M, Johnston SA, May RC, Soldati T, Machesky LM, Insall RH (2011) Actin polymerization driven by WASH causes V-ATPase retrieval and vesicle neutralization before exocytosis. J Cell Biol 193(5):831–839. https://doi.org/10.1083/jcb.201009119
Carroll B, Dunlop EA (2017) The lysosome: a crucial hub for AMPK and mTORC1 signalling. Biochem J 474(9):1453–1466. https://doi.org/10.1042/BCJ20160780
Castellano BM, Thelen AM, Moldavski O, Feltes M, van der Welle RE, Mydock-McGrane L, Jiang X, van Eijkeren RJ, Davis OB, Louie SM, Perera RM, Covey DF, Nomura DK, Ory DS, Zoncu R (2017) Lysosomal cholesterol activates mTORC1 via an SLC38A9-Niemann-Pick C1 signaling complex. Science 355(6331):1306–1311. https://doi.org/10.1126/science.aag1417
Castro-Gomes T, Corrotte M, Tam C, Andrews NW (2016) Plasma membrane repair is regulated extracellularly by proteases released from lysosomes. PLoS ONE 11(3):e0152583. https://doi.org/10.1371/journal.pone.0152583
Chantranupong L, Scaria SM, Saxton RA, Gygi MP, Shen K, Wyant GA, Wang T, Harper JW, Gygi SP, Sabatini DM (2016) The CASTOR proteins are arginine sensors for the mTORC1 pathway. Cell 165(1):153–164. https://doi.org/10.1016/j.cell.2016.02.035
Chou HT, Dukovski D, Chambers MG, Reinisch KM, Walz T (2016) CATCHR, HOPS and CORVET tethering complexes share a similar architecture. Nat Struct Mol Biol 23(8):761–763. https://doi.org/10.1038/nsmb.3264 nsmb.3264 [pii]
Christensen KA, Myers JT, Swanson JA (2002) pH-dependent regulation of lysosomal calcium in macrophages. J Cell Sci 115(Pt 3):599–607
Clapper DL, Walseth TF, Dargie PJ, Lee HC (1987) Pyridine nucleotide metabolites stimulate calcium release from sea urchin egg microsomes desensitized to inositol trisphosphate. J Biol Chem 262(20):9561–9568
Colacurcio DJ, Nixon RA (2016) Disorders of lysosomal acidification-The emerging role of v-ATPase in aging and neurodegenerative disease. Ageing Res Rev 32:75–88. https://doi.org/10.1016/j.arr.2016.05.004
Coonrod EM, Graham LA, Carpp LN, Carr TM, Stirrat L, Bowers K, Bryant NJ, Stevens TH (2013) Homotypic vacuole fusion in yeast requires organelle acidification and not the V-ATPase membrane domain. Dev Cell 27(4):462–468. https://doi.org/10.1016/j.devcel.2013.10.014
de Duve C (2005) The lysosome turns fifty. Nat Cell Biol 7(9):847–849. https://doi.org/10.1038/ncb0905-847 ncb0905-847 [pii]
De Leo MG, Staiano L, Vicinanza M, Luciani A, Carissimo A, Mutarelli M, Di Campli A, Polishchuk E, Di Tullio G, Morra V, Levtchenko E, Oltrabella F, Starborg T, Santoro M, di Bernardo D, Devuyst O, Lowe M, Medina DL, Ballabio A, De Matteis MA (2016) Autophagosome-lysosome fusion triggers a lysosomal response mediated by TLR9 and controlled by OCRL. Nat Cell Biol 18(8):839–850. https://doi.org/10.1038/ncb3386
De Luca M, Cogli L, Progida C, Nisi V, Pascolutti R, Sigismund S, Di Fiore PP, Bucci C (2014) RILP regulates vacuolar ATPase through interaction with the V1G1 subunit. J Cell Sci 127(Pt 12):2697–2708. https://doi.org/10.1242/jcs.142604
Demetriades C, Doumpas N, Teleman AA (2014) Regulation of TORC1 in response to amino acid starvation via lysosomal recruitment of TSC2. Cell 156(4):786–799. https://doi.org/10.1016/j.cell.2014.01.024
Demetriades C, Plescher M, Teleman AA (2016) Lysosomal recruitment of TSC2 is a universal response to cellular stress. Nat Commun 7:10662. https://doi.org/10.1038/ncomms10662
Desfougeres Y, Vavassori S, Rompf M, Gerasimaite R, Mayer A (2016) Organelle acidification negatively regulates vacuole membrane fusion in vivo. Sci Rep 6:29045. https://doi.org/10.1038/srep29045
Diao J, Liu R, Rong Y, Zhao M, Zhang J, Lai Y, Zhou Q, Wilz LM, Li J, Vivona S, Pfuetzner RA, Brunger AT, Zhong Q (2015) ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes. Nature 520(7548):563–566. https://doi.org/10.1038/nature14147
Dibble CC, Elis W, Menon S, Qin W, Klekota J, Asara JM, Finan PM, Kwiatkowski DJ, Murphy LO, Manning BD (2012) TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1. Mol Cell 47(4):535–546. https://doi.org/10.1016/j.molcel.2012.06.009
Dong XP, Shen D, Wang X, Dawson T, Li X, Zhang Q, Cheng X, Zhang Y, Weisman LS, Delling M, Xu H (2010) PI(3,5)P(2) controls membrane trafficking by direct activation of mucolipin Ca2+ release channels in the endolysosome. Nat Commun 1:38. https://doi.org/10.1038/ncomms1037
Dove SK, Dong K, Kobayashi T, Williams FK, Michell RH (2009) Phosphatidylinositol 3,5-bisphosphate and Fab1p/PIKfyve underPPIn endo-lysosome function. Biochem J 419(1):1–13. https://doi.org/10.1042/BJ20081950
Du X, Kumar J, Ferguson C, Schulz TA, Ong YS, Hong W, Prinz WA, Parton RG, Brown AJ, Yang H (2011) A role for oxysterol-binding protein-related protein 5 in endosomal cholesterol trafficking. J Cell Biol 192(1):121–135. https://doi.org/10.1083/jcb.201004142
Du W, Su QP, Chen Y, Zhu Y, Jiang D, Rong Y, Zhang S, Zhang Y, Ren H, Zhang C, Wang X, Gao N, Wang Y, Sun L, Sun Y, Yu L (2016) Kinesin 1 drives autolysosome tubulation. Dev Cell 37(4):326–336. https://doi.org/10.1016/j.devcel.2016.04.014
Ebner M, Lucic I, Leonard TA, Yudushkin I (2017) PI(3,4,5)P3 engagement restricts Akt activity to cellular membranes. Mol Cell 65(3):416–431(e416). https://doi.org/10.1016/j.molcel.2016.12.028
Edgar JR, Eden ER, Futter CE (2014) Hrs- and CD63-dependent competing mechanisms make different sized endosomal intraluminal vesicles. Traffic 15(2):197–211. https://doi.org/10.1111/tra.12139
Eltschinger S, Loewith R (2016) TOR complexes and the maintenance of cellular homeostasis. Trends Cell Biol 26(2):148–159. https://doi.org/10.1016/j.tcb.2015.10.003
Fader CM, Sanchez DG, Mestre MB, Colombo MI (2009) TI-VAMP/VAMP7 and VAMP3/cellubrevin: two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways. Biochim Biophys Acta 1793(12):1901–1916. https://doi.org/10.1016/j.bbamcr.2009.09.011 S0167-4889(09)00236-5 [pii]
Feng Y, He D, Yao Z, Klionsky DJ (2014) The machinery of macroautophagy. Cell Res 24(1):24–41. https://doi.org/10.1038/cr.2013.168 cr2013168 [pii]
Folick A, Oakley HD, Yu Y, Armstrong EH, Kumari M, Sanor L, Moore DD, Ortlund EA, Zechner R, Wang MC (2015) Aging. Lysosomal signaling molecules regulate longevity in Caenorhabditis elegans. Science 347(6217):83–86. https://doi.org/10.1126/science.1258857
Folts CJ, Scott-Hewitt N, Proschel C, Mayer-Proschel M, Noble M (2016) Lysosomal re-acidification prevents lysosphingolipid-induced lysosomal impairment and cellular toxicity. PLoS Biol 14(12):e1002583. https://doi.org/10.1371/journal.pbio.1002583
Fraldi A, Annunziata F, Lombardi A, Kaiser HJ, Medina DL, Spampanato C, Fedele AO, Polishchuk R, Sorrentino NC, Simons K, Ballabio A (2010) Lysosomal fusion and SNARE function are impaired by cholesterol accumulation in lysosomal storage disorders. EMBO J 29(21):3607–3620. https://doi.org/10.1038/emboj.2010.237
Friedman JR, Lackner LL, West M, DiBenedetto JR, Nunnari J, Voeltz GK (2011) ER tubules mark sites of mitochondrial division. Science 334(6054):358–362. https://doi.org/10.1126/science.1207385
Fujiwara T, Ye S, Castro-Gomes T, Winchell CG, Andrews NW, Voth DE, Varughese KI, Mackintosh SG, Feng Y, Pavlos N, Nakamura T, Manolagas SC, Zhao H (2016) PLEKHM1/DEF8/RAB7 complex regulates lysosome positioning and bone homeostasis. JCI Insight 1(17):e86330. https://doi.org/10.1172/jci.insight.86330
Garrity AG, Wang W, Collier CM, Levey SA, Gao Q, Xu H (2016) The endoplasmic reticulum, not the pH gradient, drives calcium refilling of lysosomes. Elife 5. https://doi.org/10.7554/elife.15887
Gatta AT, Levine TP (2016) Piecing Together the Patchwork of Contact Sites. Trends Cell Biol. https://doi.org/10.1016/j.tcb.2016.08.010
Goh LK, Sorkin A (2013) Endocytosis of receptor tyrosine kinases. Cold Spring Harb Perspect Biol 5(5):a017459. https://doi.org/10.1101/cshperspect.a017459 a017459, 5/5/a017459 [pii]
Goldman SD, Krise JP (2010) Niemann-Pick C1 functions independently of Niemann-Pick C2 in the initial stage of retrograde transport of membrane-impermeable lysosomal cargo. J Biol Chem 285(7):4983–4994. https://doi.org/10.1074/jbc.M109.037622
Gowrishankar S, Ferguson SM (2016) Lysosomes relax in the cellular suburbs. J Cell Biol 212(6):617–619. https://doi.org/10.1083/jcb.201602082
Grimm C, Holdt LM, Chen CC, Hassan S, Muller C, Jors S, Cuny H, Kissing S, Schroder B, Butz E, Northoff B, Castonguay J, Luber CA, Moser M, Spahn S, Lullmann-Rauch R, Fendel C, Klugbauer N, Griesbeck O, Haas A, Mann M, Bracher F, Teupser D, Saftig P, Biel M, Wahl-Schott C (2014) High susceptibility to fatty liver disease in two-pore channel 2-deficient mice. Nat Commun 5:4699. https://doi.org/10.1038/ncomms5699
Guardia CM, Farias GG, Jia R, Pu J, Bonifacino JS (2016) BORC functions upstream of kinesins 1 and 3 to coordinate regional movement of lysosomes along different microtubule tracks. Cell Rep 17(8):1950–1961. https://doi.org/10.1016/j.celrep.2016.10.062
Guo B, Liang Q, Li L, Hu Z, Wu F, Zhang P, Ma Y, Zhao B, Kovacs AL, Zhang Z, Feng D, Chen S, Zhang H (2014) O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation. Nat Cell Biol 16(12):1215–1226. https://doi.org/10.1038/ncb3066
Hamalisto S, Jaattela M (2016) Lysosomes in cancer-living on the edge (of the cell). Curr Opin Cell Biol 39:69–76. https://doi.org/10.1016/j.ceb.2016.02.009
Hammond GR, Takasuga S, Sasaki T, Balla T (2015) The ML1Nx2 phosphatidylinositol 3,5-bisphosphate probe shows poor selectivity in cells. PLoS ONE 10(10):e0139957. https://doi.org/10.1371/journal.pone.0139957
Hariri H, Ugrankar R, Liu Y, Henne WM (2016) Inter-organelle ER-endolysosomal contact sites in metabolism and disease across evolution. Commun Integr Biol 9(3):e1156278. https://doi.org/10.1080/19420889.2016.1156278
Hickey CM, Wickner W (2010) HOPS initiates vacuole docking by tethering membranes before trans-SNARE complex assembly. Mol Biol Cell 21(13):2297–2305. https://doi.org/10.1091/mbc.E10-01-0044 E10-01-0044 [pii]
Hirst J, Edgar JR, Esteves T, Darios F, Madeo M, Chang J, Roda RH, Durr A, Anheim M, Gellera C, Li J, Zuchner S, Mariotti C, Stevanin G, Blackstone C, Kruer MC, Robinson MS (2015) Loss of AP-5 results in accumulation of aberrant endolysosomes: defining a new type of lysosomal storage disease. Hum Mol Genet 24(17):4984–4996. https://doi.org/10.1093/hmg/ddv220
Holland P, Torgersen ML, Sandvig K, Simonsen A (2014) LYST affects lysosome size and quantity, but not trafficking or degradation through autophagy or endocytosis. Traffic 15(12):1390–1405. https://doi.org/10.1111/tra.12227
Huotari J, Helenius A (2011) Endosome maturation. EMBO J 30(17):3481–3500. https://doi.org/10.1038/emboj.2011.286 emboj2011286 [pii]
Inoki K, Zhu T, Guan KL (2003) TSC2 mediates cellular energy response to control cell growth and survival. Cell 115(5):577–590
Itakura E, Kishi-Itakura C, Mizushima N (2012) The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes. Cell 151(6):1256–1269. https://doi.org/10.1016/j.cell.2012.11.001 S0092-8674(12)01336-0 [pii]
Jiang P, Nishimura T, Sakamaki Y, Itakura E, Hatta T, Natsume T, Mizushima N (2014) The HOPS complex mediates autophagosome-lysosome fusion through interaction with syntaxin 17. Mol Biol Cell 25(8):1327–1337. https://doi.org/10.1091/mbc.E13-08-0447
Jin N, Lang MJ, Weisman LS (2016) Phosphatidylinositol 3,5-bisphosphate: regulation of cellular events in space and time. Biochem Soc Trans 44(1):177–184. https://doi.org/10.1042/BST20150174
Johnson DE, Ostrowski P, Jaumouille V, Grinstein S (2016) The position of lysosomes within the cell determines their luminal pH. J Cell Biol 212(6):677–692. https://doi.org/10.1083/jcb.201507112
Jongsma ML, Berlin I, Wijdeven RH, Janssen L, Janssen GM, Garstka MA, Janssen H, Mensink M, van Veelen PA, Spaapen RM, Neefjes J (2016) An ER-associated pathway defines endosomal architecture for controlled cargo transport. Cell 166(1):152–166. https://doi.org/10.1016/j.cell.2016.05.078
Jordens I, Fernandez-Borja M, Marsman M, Dusseljee S, Janssen L, Calafat J, Janssen H, Wubbolts R, Neefjes J (2001) The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein-dynactin motors. Curr Biol 11(21):1680–1685
Jung J, Genau HM, Behrends C (2015) Amino acid-dependent mTORC1 regulation by the lysosomal Membrane protein SLC38A9. Mol Cell Biol 35(14):2479–2494. https://doi.org/10.1128/MCB.00125-15
Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11(5):373–384. https://doi.org/10.1038/ni.1863
Khatter D, Raina VB, Dwivedi D, Sindhwani A, Bahl S, Sharma M (2015) The small GTPase Arl8b regulates assembly of the mammalian HOPS complex on lysosomes. J Cell Sci 128(9):1746–1761. https://doi.org/10.1242/jcs.162651 jcs.162651 [pii]
Kim J, Kundu M, Viollet B, Guan KL (2011) AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 13(2):132–141. https://doi.org/10.1038/ncb2152
Kim YM, Jung CH, Seo M, Kim EK, Park JM, Bae SS, Kim DH (2015) mTORC1 phosphorylates UVRAG to negatively regulate autophagosome and endosome maturation. Mol Cell 57(2):207–218. https://doi.org/10.1016/j.molcel.2014.11.013
Korolchuk VI, Saiki S, Lichtenberg M, Siddiqi FH, Roberts EA, Imarisio S, Jahreiss L, Sarkar S, Futter M, Menzies FM, O’Kane CJ, Deretic V, Rubinsztein DC (2011) Lysosomal positioning coordinates cellular nutrient responses. Nat Cell Biol 13(4):453–460. https://doi.org/10.1038/ncb2204
Kruppa AJ, Kendrick-Jones J, Buss F (2016) Myosins, actin and autophagy. Traffic 17(8):878–890. https://doi.org/10.1111/tra.12410
Laplante M, Sabatini DM (2012) mTOR signaling in growth control and disease. Cell 149(2):274–293. https://doi.org/10.1016/j.cell.2012.03.017
Lassen KG, McKenzie CI, Mari M, Murano T, Begun J, Baxt LA, Goel G, Villablanca EJ, Kuo SY, Huang H, Macia L, Bhan AK, Batten M, Daly MJ, Reggiori F, Mackay CR, Xavier RJ (2016) Genetic coding variant in GPR65 alters lysosomal pH and links lysosomal dysfunction with colitis risk. Immunity 44(6):1392–1405. https://doi.org/10.1016/j.immuni.2016.05.007
Li X, Wang X, Zhang X, Zhao M, Tsang WL, Zhang Y, Yau RG, Weisman LS, Xu H (2013) Genetically encoded fluorescent probe to visualize intracellular phosphatidylinositol 3,5-bisphosphate localization and dynamics. Proc Natl Acad Sci U S A 110(52):21165–21170. https://doi.org/10.1073/pnas.1311864110
Li SC, Diakov TT, Xu T, Tarsio M, Zhu W, Couoh-Cardel S, Weisman LS, Kane PM (2014) The signaling lipid PI(3,5)P(2) stabilizes V(1)-V(0) sector interactions and activates the V-ATPase. Mol Biol Cell 25(8):1251–1262. https://doi.org/10.1091/mbc.E13-10-0563
Li Y, Xu M, Ding X, Yan C, Song Z, Chen L, Huang X, Wang X, Jian Y, Tang G, Tang C, Di Y, Mu S, Liu X, Liu K, Li T, Wang Y, Miao L, Guo W, Hao X, Yang C (2016) Protein kinase C controls lysosome biogenesis independently of mTORC1. Nat Cell Biol 18(10):1065–1077. https://doi.org/10.1038/ncb3407
Lim CY, Zoncu R (2016) The lysosome as a command-and-control center for cellular metabolism. J Cell Biol 214(6):653–664. https://doi.org/10.1083/jcb.201607005
Lin X, Yang T, Wang S, Wang Z, Yun Y, Sun L, Zhou Y, Xu X, Akazawa C, Hong W, Wang T (2014) RILP interacts with HOPS complex via VPS41 subunit to regulate endocytic trafficking. Sci Rep 4:7282. https://doi.org/10.1038/srep07282 srep07282 [pii]
Lloyd-Evans E, Platt FM (2011) Lysosomal Ca2+ homeostasis: role in pathogenesis of lysosomal storage diseases. Cell Calcium 50(2):200–205. https://doi.org/10.1016/j.ceca.2011.03.010
Lloyd-Evans E, Morgan AJ, He X, Smith DA, Elliot-Smith E, Sillence DJ, Churchill GC, Schuchman EH, Galione A, Platt FM (2008) Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium. Nat Med 14(11):1247–1255. https://doi.org/10.1038/nm.1876
Lopez-Sanjurjo CI, Tovey SC, Prole DL, Taylor CW (2013) Lysosomes shape Ins(1,4,5)P3-evoked Ca2+ signals by selectively sequestering Ca2+ released from the endoplasmic reticulum. J Cell Sci 126(Pt 1):289–300. https://doi.org/10.1242/jcs.116103
Luzio JP, Pryor PR, Bright NA (2007) Lysosomes: fusion and function. Nat Rev Mol Cell Biol 8(8):622–632. https://doi.org/10.1038/nrm2217 nrm2217 [pii]
Luzio JP, Hackmann Y, Dieckmann NM, Griffiths GM (2014) The biogenesis of lysosomes and lysosome-related organelles. Cold Spring Harb Perspect Biol 6(9):a016840. https://doi.org/10.1101/cshperspect.a016840 a016840, 6/9/a016840 [pii]
MacDonald C, Stamnes MA, Katzmann DJ, Piper RC (2015) Tetraspan cargo adaptors usher GPI-anchored proteins into multivesicular bodies. Cell Cycle 14(23):3673–3678. https://doi.org/10.1080/15384101.2015.1100773
Majer O, Liu B, Barton GM (2016) Nucleic acid-sensing TLRs: trafficking and regulation. Curr Opin Immunol 44:26–33. https://doi.org/10.1016/j.coi.2016.10.003
Manifava M, Smith M, Rotondo S, Walker S, Niewczas I, Zoncu R, Clark J, Ktistakis NT (2016) Dynamics of mTORC1 activation in response to amino acids. Elife 5. https://doi.org/10.7554/elife.19960
Martens S, Nakamura S, Yoshimori T (2016) Phospholipids in autophagosome formation and fusion. J Mol Biol. https://doi.org/10.1016/j.jmb.2016.10.029
Martina JA, Puertollano R (2013) Rag GTPases mediate amino acid-dependent recruitment of TFEB and MITF to lysosomes. J Cell Biol 200(4):475–491. https://doi.org/10.1083/jcb.201209135
Martina JA, Diab HI, Brady OA, Puertollano R (2016) TFEB and TFE3 are novel components of the integrated stress response. EMBO J 35(5):479–495. https://doi.org/10.15252/embj.201593428
Marwaha R, Arya SB, Jagga D, Kaur H, Tuli A, Sharma M (2017) The Rab7 effector PLEKHM1 binds Arl8b to promote cargo traffic to lysosomes. J Cell Biol 216(4):1051–1070. https://doi.org/10.1083/jcb.201607085
Mauvezin C, Nagy P, Juhasz G, Neufeld TP (2015) Autophagosome-lysosome fusion is independent of V-ATPase-mediated acidification. Nat Commun 6:7007. https://doi.org/10.1038/ncomms8007
McEwan DG, Dikic I (2015) PLEKHM1: adapting to life at the lysosome. Autophagy 11(4):720–722. https://doi.org/10.1080/15548627.2015.1034419
McEwan DG, Popovic D, Gubas A, Terawaki S, Suzuki H, Stadel D, Coxon FP, Miranda de Stegmann D, Bhogaraju S, Maddi K, Kirchof A, Gatti E, Helfrich MH, Wakatsuki S, Behrends C, Pierre P, Dikic I (2015) PLEKHM1 regulates autophagosome-lysosome fusion through HOPS complex and LC3/GABARAP proteins. Mol Cell 57(1):39–54. https://doi.org/10.1016/j.molcel.2014.11.006
Medina DL, Fraldi A, Bouche V, Annunziata F, Mansueto G, Spampanato C, Puri C, Pignata A, Martina JA, Sardiello M, Palmieri M, Polishchuk R, Puertollano R, Ballabio A (2011) Transcriptional activation of lysosomal exocytosis promotes cellular clearance. Dev Cell 21(3):421–430. https://doi.org/10.1016/j.devcel.2011.07.016
Medina DL, Di Paola S, Peluso I, Armani A, De Stefani D, Venditti R, Montefusco S, Scotto-Rosato A, Prezioso C, Forrester A, Settembre C, Wang W, Gao Q, Xu H, Sandri M, Rizzuto R, De Matteis MA, Ballabio A (2015) Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB. Nat Cell Biol 17(3):288–299. https://doi.org/10.1038/ncb3114
Melchionda M, Pittman JK, Mayor R, Patel S (2016) Ca2+/H+ exchange by acidic organelles regulates cell migration in vivo. J Cell Biol 212(7):803–813. https://doi.org/10.1083/jcb.201510019
Menon S, Dibble CC, Talbott G, Hoxhaj G, Valvezan AJ, Takahashi H, Cantley LC, Manning BD (2014) Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome. Cell 156(4):771–785. https://doi.org/10.1016/j.cell.2013.11.049
Metcalf D, Isaacs AM (2010) The role of ESCRT proteins in fusion events involving lysosomes, endosomes and autophagosomes. Biochem Soc Trans 38(6):1469–1473. https://doi.org/10.1042/BST0381469
Miller A, Schafer J, Upchurch C, Spooner E, Huynh J, Hernandez S, McLaughlin B, Oden L, Fares H (2015) Mucolipidosis type IV protein TRPML1-dependent lysosome formation. Traffic 16(3):284–297. https://doi.org/10.1111/tra.12249
Morgan AJ, Platt FM, Lloyd-Evans E, Galione A (2011) Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease. Biochem J 439(3):349–374. https://doi.org/10.1042/BJ20110949
Napolitano G, Ballabio A (2016) TFEB at a glance. J Cell Sci 129(13):2475–2481. https://doi.org/10.1242/jcs.146365
Nguyen TN, Padman BS, Usher J, Oorschot V, Ramm G, Lazarou M (2016) Atg8 family LC3/GABARAP proteins are crucial for autophagosome-lysosome fusion but not autophagosome formation during PINK1/Parkin mitophagy and starvation. J Cell Biol 215(6):857–874. https://doi.org/10.1083/jcb.201607039
Nguyen ON, Grimm C, Schneider LS, Chao YK, Atzberger C, Bartel K, Watermann A, Ulrich M, Mayr D, Wahl-Schott C, Biel M, Vollmar AM (2017) Two-pore channel function is crucial for migration of invasive cancer cells. Cancer Res. https://doi.org/10.1158/0008-5472.CAN-16-0852
Palmieri M, Impey S, Kang H, di Ronza A, Pelz C, Sardiello M, Ballabio A (2011) Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways. Hum Mol Genet 20(19):3852–3866. https://doi.org/10.1093/hmg/ddr306
Palmieri M, Pal R, Nelvagal HR, Lotfi P, Stinnett GR, Seymour ML, Chaudhury A, Bajaj L, Bondar VV, Bremner L, Saleem U, Tse DY, Sanagasetti D, Wu SM, Neilson JR, Pereira FA, Pautler RG, Rodney GG, Cooper JD, Sardiello M (2017) mTORC1-independent TFEB activation via Akt inhibition promotes cellular clearance in neurodegenerative storage diseases. Nat Commun 8:14338. https://doi.org/10.1038/ncomms14338
Parra KJ, Kane PM (1998) Reversible association between the V1 and V0 domains of yeast vacuolar H+ -ATPase is an unconventional glucose-induced effect. Mol Cell Biol 18(12):7064–7074
Peng M, Yin N, Li MO (2017) SZT2 dictates GATOR control of mTORC1 signalling. Nature. https://doi.org/10.1038/nature21378
Penny CJ, Kilpatrick BS, Eden ER, Patel S (2015) Coupling acidic organelles with the ER through Ca2+ microdomains at membrane contact sites. Cell Calcium 58(4):387–396. https://doi.org/10.1016/j.ceca.2015.03.006
Perera RM, Zoncu R (2016) The lysosome as a regulatory hub. Annu Rev Cell Dev Biol 32:223–253. https://doi.org/10.1146/annurev-cellbio-111315-125125
Petit CS, Roczniak-Ferguson A, Ferguson SM (2013) Recruitment of folliculin to lysosomes supports the amino acid-dependent activation of Rag GTPases. J Cell Biol 202(7):1107–1122. https://doi.org/10.1083/jcb.201307084
Pislar A, Perisic Nanut M, Kos J (2015) Lysosomal cysteine peptidases—molecules signaling tumor cell death and survival. Semin Cancer Biol 35:168–179. https://doi.org/10.1016/j.semcancer.2015.08.001
Pitt SJ, Funnell TM, Sitsapesan M, Venturi E, Rietdorf K, Ruas M, Ganesan A, Gosain R, Churchill GC, Zhu MX, Parrington J, Galione A, Sitsapesan R (2010) TPC2 is a novel NAADP-sensitive Ca2+ release channel, operating as a dual sensor of luminal pH and Ca2+. J Biol Chem 285(45):35039–35046. https://doi.org/10.1074/jbc.M110.156927
Platt FM, Boland B, van der Spoel AC (2012) The cell biology of disease: lysosomal storage disorders: the cellular impact of lysosomal dysfunction. J Cell Biol 199(5):723–734. https://doi.org/10.1083/jcb.201208152
Platta HW, Stenmark H (2011) Endocytosis and signaling. Curr Opin Cell Biol 23(4):393–403. https://doi.org/10.1016/j.ceb.2011.03.008 S0955-0674(11)00025-1 [pii]
Pols MS, ten Brink C, Gosavi P, Oorschot V, Klumperman J (2013) The HOPS proteins hVps41 and hVps39 are required for homotypic and heterotypic late endosome fusion. Traffic 14(2):219–232. https://doi.org/10.1111/tra.12027
Pryor PR, Mullock BM, Bright NA, Gray SR, Luzio JP (2000) The role of intraorganellar Ca2+ in late endosome-lysosome heterotypic fusion and in the reformation of lysosomes from hybrid organelles. J Cell Biol 149(5):1053–1062
Pryor PR, Mullock BM, Bright NA, Lindsay MR, Gray SR, Richardson SC, Stewart A, James DE, Piper RC, Luzio JP (2004) Combinatorial SNARE complexes with VAMP7 or VAMP8 define different late endocytic fusion events. EMBO Rep 5(6):590–595. https://doi.org/10.1038/sj.embor.7400150 7400150 [pii]
Pu J, Schindler C, Jia R, Jarnik M, Backlund P, Bonifacino JS (2015) BORC, a multisubunit complex that regulates lysosome positioning. Dev Cell 33(2):176–188. https://doi.org/10.1016/j.devcel.2015.02.011
Raben N, Puertollano R (2016) TFEB and TFE3: linking lysosomes to cellular adaptation to stress. Annu Rev Cell Dev Biol 32:255–278. https://doi.org/10.1146/annurev-cellbio-111315-125407
Raffaello A, Mammucari C, Gherardi G, Rizzuto R (2016) Calcium at the center of cell signaling: interplay between endoplasmic reticulum, mitochondria, and lysosomes. Trends Biochem Sci 41(12):1035–1049. https://doi.org/10.1016/j.tibs.2016.09.001
Rao SK, Huynh C, Proux-Gillardeaux V, Galli T, Andrews NW (2004) Identification of SNAREs involved in synaptotagmin VII-regulated lysosomal exocytosis. J Biol Chem 279(19):20471–20479. https://doi.org/10.1074/jbc.M400798200
Rebsamen M, Pochini L, Stasyk T, de Araujo ME, Galluccio M, Kandasamy RK, Snijder B, Fauster A, Rudashevskaya EL, Bruckner M, Scorzoni S, Filipek PA, Huber KV, Bigenzahn JW, Heinz LX, Kraft C, Bennett KL, Indiveri C, Huber LA, Superti-Furga G (2015) SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1. Nature 519(7544):477–481. https://doi.org/10.1038/nature14107
Roczniak-Ferguson A, Petit CS, Froehlich F, Qian S, Ky J, Angarola B, Walther TC, Ferguson SM (2012) The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis. Sci Signal 5(228):ra42. https://doi.org/10.1126/scisignal.2002790
Ronco V, Potenza DM, Denti F, Vullo S, Gagliano G, Tognolina M, Guerra G, Pinton P, Genazzani AA, Mapelli L, Lim D, Moccia F (2015) A novel Ca2+-mediated cross-talk between endoplasmic reticulum and acidic organelles: implications for NAADP-dependent Ca2+ signalling. Cell Calcium 57(2):89–100. https://doi.org/10.1016/j.ceca.2015.01.001
Rong Y, McPhee CK, Deng S, Huang L, Chen L, Liu M, Tracy K, Baehrecke EH, Yu L, Lenardo MJ (2011) Spinster is required for autophagic lysosome reformation and mTOR reactivation following starvation. Proc Natl Acad Sci U S A 108(19):7826–7831. https://doi.org/10.1073/pnas.1013800108
Rong Y, Liu M, Ma L, Du W, Zhang H, Tian Y, Cao Z, Li Y, Ren H, Zhang C, Li L, Chen S, Xi J, Yu L (2012) Clathrin and phosphatidylinositol-4,5-bisphosphate regulate autophagic lysosome reformation. Nat Cell Biol 14(9):924–934. https://doi.org/10.1038/ncb2557
Rosa-Ferreira C, Munro S (2011) Arl8 and SKIP act together to link lysosomes to kinesin-1. Dev Cell 21(6):1171–1178. https://doi.org/10.1016/j.devcel.2011.10.007
Rowland AA, Chitwood PJ, Phillips MJ, Voeltz GK (2014) ER contact sites define the position and timing of endosome fission. Cell 159(5):1027–1041. https://doi.org/10.1016/j.cell.2014.10.023
Saarikangas J, Zhao H, Lappalainen P (2010) Regulation of the actin cytoskeleton-plasma membrane interplay by phosphoinositides. Physiol Rev 90(1):259–289. https://doi.org/10.1152/physrev.00036.2009
Sakurai Y, Kolokoltsov AA, Chen CC, Tidwell MW, Bauta WE, Klugbauer N, Grimm C, Wahl-Schott C, Biel M, Davey RA (2015) Ebola virus. Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment. Science 347(6225):995–998. https://doi.org/10.1126/science.1258758
Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC, Bar-Peled L, Sabatini DM (2008) The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320(5882):1496–1501. https://doi.org/10.1126/science.1157535 1157535 [pii]
Sardiello M, Palmieri M, di Ronza A, Medina DL, Valenza M, Gennarino VA, Di Malta C, Donaudy F, Embrione V, Polishchuk RS, Banfi S, Parenti G, Cattaneo E, Ballabio A (2009) A gene network regulating lysosomal biogenesis and function. Science 325(5939):473–477. https://doi.org/10.1126/science.1174447 1174447 [pii]
Sargeant TJ, Lloyd-Lewis B, Resemann HK, Ramos-Montoya A, Skepper J, Watson CJ (2014) Stat3 controls cell death during mammary gland involution by regulating uptake of milk fat globules and lysosomal membrane permeabilization. Nat Cell Biol 16(11):1057–1068. https://doi.org/10.1038/ncb3043
Sbano L, Bonora M, Marchi S, Baldassari F, Medina DL, Ballabio A, Giorgi C, Pinton P (2017) TFEB-mediated increase in peripheral lysosomes regulates store-operated calcium entry. Sci Rep 7:40797. https://doi.org/10.1038/srep40797
Schafer IB, Hesketh GG, Bright NA, Gray SR, Pryor PR, Evans PR, Luzio JP, Owen DJ (2012) The binding of Varp to VAMP7 traps VAMP7 in a closed, fusogenically inactive conformation. Nat Struct Mol Biol 19(12):1300–1309. https://doi.org/10.1038/nsmb.2414
Schmid JA, Mach L, Paschke E, Glossl J (1999) Accumulation of sialic acid in endocytic compartments interferes with the formation of mature lysosomes. Impaired proteolytic processing of cathepsin B in fibroblasts of patients with lysosomal sialic acid storage disease. J Biol Chem 274(27):19063–19071
Schulze RJ, Weller SG, Schroeder B, Krueger EW, Chi S, Casey CA, McNiven MA (2013) Lipid droplet breakdown requires dynamin 2 for vesiculation of autolysosomal tubules in hepatocytes. J Cell Biol 203(2):315–326. https://doi.org/10.1083/jcb.201306140
Seaman MN, Ball CL, Robinson MS (1993) Targeting and mistargeting of plasma membrane adaptors in vitro. J Cell Biol 123(5):1093–1105
Sengupta S, Peterson TR, Sabatini DM (2010) Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell 40(2):310–322. https://doi.org/10.1016/j.molcel.2010.09.026
Serrano-Puebla A, Boya P (2016) Lysosomal membrane permeabilization in cell death: new evidence and implications for health and disease. Ann N Y Acad Sci 1371(1):30–44. https://doi.org/10.1111/nyas.12966
Settembre C, Zoncu R, Medina DL, Vetrini F, Erdin S, Huynh T, Ferron M, Karsenty G, Vellard MC, Facchinetti V, Sabatini DM, Ballabio A (2012) A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. EMBO J 31(5):1095–1108. https://doi.org/10.1038/emboj.2012.32 emboj201232 [pii]
Settembre C, De Cegli R, Mansueto G, Saha PK, Vetrini F, Visvikis O, Huynh T, Carissimo A, Palmer D, Klisch TJ, Wollenberg AC, Di Bernardo D, Chan L, Irazoqui JE, Ballabio A (2013a) TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop. Nat Cell Biol 15(6):647–658. https://doi.org/10.1038/ncb2718
Settembre C, Fraldi A, Medina DL, Ballabio A (2013b) Signals from the lysosome: a control centre for cellular clearance and energy metabolism. Nat Rev Mol Cell Biol 14(5):283–296. https://doi.org/10.1038/nrm3565
Sonenberg N, Hinnebusch AG (2009) Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 136(4):731–745. https://doi.org/10.1016/j.cell.2009.01.042
Sorkin A, Goh LK (2008) Endocytosis and intracellular trafficking of ErbBs. Exp Cell Res 314(17):3093–3106. https://doi.org/10.1016/j.yexcr.2008.08.013
Spampanato C, Feeney E, Li L, Cardone M, Lim JA, Annunziata F, Zare H, Polishchuk R, Puertollano R, Parenti G, Ballabio A, Raben N (2013) Transcription factor EB (TFEB) is a new therapeutic target for Pompe disease. EMBO Mol Med 5(5):691–706. https://doi.org/10.1002/emmm.201202176
Steger M, Tonelli F, Ito G, Davies P, Trost M, Vetter M, Wachter S, Lorentzen E, Duddy G, Wilson S, Baptista MA, Fiske BK, Fell MJ, Morrow JA, Reith AD, Alessi DR, Mann M (2016) Phosphoproteomics reveals that Parkinson’s disease kinase LRRK2 regulates a subset of Rab GTPases. Elife 5. https://doi.org/10.7554/elife.12813
Steinberg BE, Huynh KK, Brodovitch A, Jabs S, Stauber T, Jentsch TJ, Grinstein S (2010) A cation counterflux supports lysosomal acidification. J Cell Biol 189(7):1171–1186. https://doi.org/10.1083/jcb.200911083
Tian X, Gala U, Zhang Y, Shang W, Nagarkar Jaiswal S, di Ronza A, Jaiswal M, Yamamoto S, Sandoval H, Duraine L, Sardiello M, Sillitoe RV, Venkatachalam K, Fan H, Bellen HJ, Tong C (2015) A voltage-gated calcium channel regulates lysosomal fusion with endosomes and autophagosomes and is required for neuronal homeostasis. PLoS Biol 13(3):e1002103. https://doi.org/10.1371/journal.pbio.1002103
Toyofuku T, Morimoto K, Sasawatari S, Kumanogoh A (2015) Leucine-Rich repeat kinase 1 regulates autophagy through turning on TBC1D2-dependent Rab7 inactivation. Mol Cell Biol 35(17):3044–3058. https://doi.org/10.1128/MCB.00085-15
Tsun ZY, Bar-Peled L, Chantranupong L, Zoncu R, Wang T, Kim C, Spooner E, Sabatini DM (2013) The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1. Mol Cell 52(4):495–505. https://doi.org/10.1016/j.molcel.2013.09.016
van der Kant R, Fish A, Janssen L, Janssen H, Krom S, Ho N, Brummelkamp T, Carette J, Rocha N, Neefjes J (2013) Late endosomal transport and tethering are coupled processes controlled by RILP and the cholesterol sensor ORP1L. J Cell Sci 126(Pt 15):3462–3474. https://doi.org/10.1242/jcs.129270
van der Kant R, Jonker CT, Wijdeven RH, Bakker J, Janssen L, Klumperman J, Neefjes J (2015) Characterization of the mammalian CORVET and HOPS complexes and their modular restructuring for endosome specificity. J Biol Chem 290(51):30280–30290. https://doi.org/10.1074/jbc.M115.688440 M115.688440 [pii]
Vega-Rubin-de-Celis S, Pena-Llopis S, Konda M, Brugarolas J (2017) Multistep regulation of TFEB by MTORC1. Autophagy. https://doi.org/10.1080/15548627.2016.1271514
Wang S, Tsun ZY, Wolfson RL, Shen K, Wyant GA, Plovanich ME, Yuan ED, Jones TD, Chantranupong L, Comb W, Wang T, Bar-Peled L, Zoncu R, Straub C, Kim C, Park J, Sabatini BL, Sabatini DM (2015) Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. Science 347(6218):188–194. https://doi.org/10.1126/science.1257132
Wang Z, Miao G, Xue X, Guo X, Yuan C, Wang Z, Zhang G, Chen Y, Feng D, Hu J, Zhang H (2016) The Vici syndrome protein EPG5 is a Rab7 effector that determines the fusion specificity of autophagosomes with late endosomes/lysosomes. Mol Cell 63(5):781–795. https://doi.org/10.1016/j.molcel.2016.08.021
Wartosch L, Gunesdogan U, Graham SC, Luzio JP (2015) Recruitment of VPS33A to HOPS by VPS16 Is required for lysosome fusion with endosomes and autophagosomes. Traffic 16(7):727–742. https://doi.org/10.1111/tra.12283
Wee YS, Roundy KM, Weis JJ, Weis JH (2012) Interferon-inducible transmembrane proteins of the innate immune response act as membrane organizers by influencing clathrin and v-ATPase localization and function. Innate Immun 18(6):834–845. https://doi.org/10.1177/1753425912443392
White IJ, Bailey LM, Aghakhani MR, Moss SE, Futter CE (2006) EGF stimulates annexin 1-dependent inward vesiculation in a multivesicular endosome subpopulation. EMBO J 25(1):1–12. https://doi.org/10.1038/sj.emboj.7600759
Wijdeven RH, Janssen H, Nahidiazar L, Janssen L, Jalink K, Berlin I, Neefjes J (2016) Cholesterol and ORP1L-mediated ER contact sites control autophagosome transport and fusion with the endocytic pathway. Nat Commun 7:11808. https://doi.org/10.1038/ncomms11808
Wolfson RL, Chantranupong L, Saxton RA, Shen K, Scaria SM, Cantor JR, Sabatini DM (2016) Sestrin2 is a leucine sensor for the mTORC1 pathway. Science 351(6268):43–48. https://doi.org/10.1126/science.aab2674
Wolfson RL, Chantranupong L, Wyant GA, Gu X, Orozco JM, Shen K, Condon KJ, Petri S, Kedir J, Scaria SM, Abu-Remaileh M, Frankel WN, Sabatini DM (2017) KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1. Nature. https://doi.org/10.1038/nature21423
Woodman PG, Futter CE (2008) Multivesicular bodies: co-ordinated progression to maturity. Curr Opin Cell Biol 20(4):408–414. https://doi.org/10.1016/j.ceb.2008.04.001 S0955-0674(08)00072-0 [pii]
Yamasaki M, Thomas JM, Churchill GC, Garnham C, Lewis AM, Cancela JM, Patel S, Galione A (2005) Role of NAADP and cADPR in the induction and maintenance of agonist-evoked Ca2+ spiking in mouse pancreatic acinar cells. Curr Biol 15(9):874–878. https://doi.org/10.1016/j.cub.2005.04.033
Yamashiro DJ, Maxfield FR (1987) Acidification of morphologically distinct endosomes in mutant and wild-type Chinese hamster ovary cells. J Cell Biol 105(6 Pt 1):2723–2733
Yu L, McPhee CK, Zheng L, Mardones GA, Rong Y, Peng J, Mi N, Zhao Y, Liu Z, Wan F, Hailey DW, Oorschot V, Klumperman J, Baehrecke EH, Lenardo MJ (2010) Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature 465(7300):942–946. https://doi.org/10.1038/nature09076
Zhang H, Hu J (2016) Shaping the Endoplasmic Reticulum into a Social Network. Trends Cell Biol 26(12):934–943. https://doi.org/10.1016/j.tcb.2016.06.002
Zhang CS, Jiang B, Li M, Zhu M, Peng Y, Zhang YL, Wu YQ, Li TY, Liang Y, Lu Z, Lian G, Liu Q, Guo H, Yin Z, Ye Z, Han J, Wu JW, Yin H, Lin SY, Lin SC (2014) The lysosomal v-ATPase-Ragulator complex is a common activator for AMPK and mTORC1, acting as a switch between catabolism and anabolism. Cell Metab 20(3):526–540. https://doi.org/10.1016/j.cmet.2014.06.014
Zoncu R, Bar-Peled L, Efeyan A, Wang S, Sancak Y, Sabatini DM (2011a) mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H+-ATPase. Science 334(6056):678–683. https://doi.org/10.1126/science.1207056
Zoncu R, Efeyan A, Sabatini DM (2011b) mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 12(1):21–35. https://doi.org/10.1038/nrm3025
Zou J, Hu B, Arpag S, Yan Q, Hamilton A, Zeng YS, Vanoye CG, Li J (2015) Reactivation of lysosomal Ca2+ efflux rescues abnormal lysosomal storage in FIG4-deficient cells. J Neurosci 35(17):6801–6812. https://doi.org/10.1523/JNEUROSCI.4442-14.2015
Acknowledgements
GGH is supported by a Basic Research Fellowship from Parkinson Canada. Recent experimental work from JPL and NAB referred to in this chapter is supported by UK MRC research grant MR/M010007/1. LJD is supported by a BBSRC industrial CASE studentship with GSK Research and Development Ltd. The Cambridge Institute for Medical Research is supported by Wellcome Trust Strategic Award 100140.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG, part of Springer Nature
About this chapter
Cite this chapter
Hesketh, G.G., Wartosch, L., Davis, L.J., Bright, N.A., Luzio, J.P. (2018). The Lysosome and Intracellular Signalling. In: Lamaze, C., Prior, I. (eds) Endocytosis and Signaling. Progress in Molecular and Subcellular Biology, vol 57. Springer, Cham. https://doi.org/10.1007/978-3-319-96704-2_6
Download citation
DOI: https://doi.org/10.1007/978-3-319-96704-2_6
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-96703-5
Online ISBN: 978-3-319-96704-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)