Dissecting the Gene Network of Dietary Restriction to Identify Evolutionarily Conserved Pathways and New Functional Genes

PLoS Genetics

Volumn 8, Issue 8, 2012, Pages

  Wuttke, Daniel ^a   Connor, Richard ^b   Vora, Chintan ^a   Craig, Thomas ^a   Li, Yang ^a,e   Wood, Shona ^a   Vasieva, Olga ^a   Shmookler Reis, Robert ^c,d   Tang, Fusheng ^b   de Magalhães, João Pedro ^a  

^a UNIVERSITY OF LIVERPOOL   (United Kingdom)

^b University of Arkansas ^*  (United States)

^c UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES   (United States)

^d UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES   (United States)

^e UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

GROWTH HORMONE RECEPTOR; SPERMIDINE; TRANSCRIPTION FACTOR;

ARTICLE; CELL VACUOLE; CONTROLLED STUDY; DELETION MUTANT; DIET RESTRICTION; ESSENTIAL GENE; FLY; FRE6 GENE; GENE EXPRESSION; GENE FUNCTION; GENE INTERACTION; GENE REGULATORY NETWORK; GENETIC CONSERVATION; GENETIC DATABASE; GENETIC IDENTIFICATION; GROWTH HORMONE RECEPTOR GENE; HUMAN; LIFE EXTENSION; LONGEVITY; MEIOSIS; MOLECULAR INTERACTION; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; OPT2 GENE; PREDICTION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; RCR2 GENE; RECEPTOR GENE; STRESS; TRANSLATION REGULATION; VALIDATION STUDY; WORM; YEAST;

AGING; ANIMALS; BIOLOGICAL EVOLUTION; CALORIC RESTRICTION; DATABASES, GENETIC; DIET; GAMETOGENESIS; GENE REGULATORY NETWORKS; GENES, ESSENTIAL; HUMANS; LIFE EXPECTANCY; LONGEVITY; MUTATION; SACCHAROMYCES CEREVISIAE; SYSTEMS BIOLOGY;

MUS; SACCHAROMYCETALES;

EID: 84866160403     PISSN: 15537390     EISSN: 15537404     Source Type: Journal    
DOI: 10.1371/journal.pgen.1002834     Document Type: Article

References (111)

1. Bishop NA, Guarente L, (2007) Genetic links between diet and lifespan: shared mechanisms from yeast to humans. Nat Rev Genet 8: 835-844.
2. Fontana L, Partridge L, Longo VD, (2010) Extending healthy life span-from yeast to humans. Science 328: 321-326.
3. Kemnitz JW, (2011) Calorie restriction and aging in nonhuman primates. ILAR J 52: 66-77.
4. Willcox BJ, Willcox DC, Todoriki H, Fujiyoshi A, Yano K, et al. (2007) Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world's longest-lived people and its potential impact on morbidity and life span. Ann N Y Acad Sci 1114: 434-455.
5. Spindler SR, (2010) Caloric restriction: from soup to nuts. Ageing Res Rev 9: 324-353.
6. de Magalhaes JP, Wuttke D, Wood SH, Plank M, Vora C, (2012) Genome-environment interactions that modulate aging: powerful targets for drug discovery. Pharmacol Rev 64: 88-101.
7. Lakowski B, Hekimi S, (1998) The genetics of caloric restriction in Caenorhabditis elegans. Proc Natl Acad Sci U S A 95: 13091-13096.
8. Partridge L, Piper MD, Mair W, (2005) Dietary restriction in Drosophila. Mech Ageing Dev 126: 938-950.
9. Barabasi AL, Gulbahce N, Loscalzo J, (2011) Network medicine: a network-based approach to human disease. Nat Rev Genet 12: 56-68.
10. de Magalhaes JP, Church GM, (2007) Analyses of human-chimpanzee orthologous gene pairs to explore evolutionary hypotheses of aging. Mech Ageing Dev 128: 355-364.
11. Budovsky A, Abramovich A, Cohen R, Chalifa-Caspi V, Fraifeld V, (2007) Longevity network: construction and implications. Mech Ageing Dev 128: 117-124.
12. Wang J, Zhang S, Wang Y, Chen L, Zhang XS, (2009) Disease-aging network reveals significant roles of aging genes in connecting genetic diseases. PLoS Comput Biol 5: e1000521 doi:10.1371/journal.pcbi.1000521.
13. Promislow DE, (2004) Protein networks, pleiotropy and the evolution of senescence. Proc Biol Sci 271: 1225-1234.
14. Witten TM, Bonchev D, (2007) Predicting aging/longevity-related genes in the nematode Caenorhabditis elegans. Chem Biodivers 4: 2639-2655.
15. Fortney K, Kotlyar M, Jurisica I, (2010) Inferring the functions of longevity genes with modular subnetwork biomarkers of Caenorhabditis elegans aging. Genome Biol 11: R13.
16. Bonkowski MS, Rocha JS, Masternak MM, Al Regaiey KA, Bartke A, (2006) Targeted disruption of growth hormone receptor interferes with the beneficial actions of calorie restriction. Proc Natl Acad Sci U S A 103: 7901-7905.
17. Gems D, Pletcher S, Partridge L, (2002) Interpreting interactions between treatments that slow aging. Aging Cell 1: 1-9.
18. de Magalhaes JP, Budovsky A, Lehmann G, Costa J, Li Y, et al. (2009) The Human Ageing Genomic Resources: online databases and tools for biogerontologists. Aging Cell 8: 65-72.
19. Shmookler Reis RJ, Ayyadevara S, Crow WA, Lee T, Delongchamp RR, (2011) Gene Categories Differentially Expressed in C. elegans Age-1 Mutants of Extraordinary Longevity: New Insights From Novel Data-Mining Procedures. J Gerontol A Biol Sci Med Sci 67: 366-75.
20. Tazearslan C, Ayyadevara S, Bharill P, Shmookler Reis RJ, (2009) Positive feedback between transcriptional and kinase suppression in nematodes with extraordinary longevity and stress resistance. PLoS Genet 5: e1000452 doi:10.1371/journal.pgen.1000452.
21. de Magalhaes JP, Toussaint O, (2004) GenAge: a genomic and proteomic network map of human ageing. FEBS Lett 571: 243-247 doi:10.1371/journal.pgen.1000452.
22. Owen AB, Stuart J, Mach K, Villeneuve AM, Kim S, (2003) A gene recommender algorithm to identify coexpressed genes in C. elegans. Genome Res 13: 1828-1837.
23. Tang F, Watkins JW, Bermudez M, Gray R, Gaban A, et al. (2008) A life-span extending form of autophagy employs the vacuole-vacuole fusion machinery. Autophagy 4: 874-886.
24. Lin SJ, Kaeberlein M, Andalis AA, Sturtz LA, Defossez PA, et al. (2002) Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature 418: 344-348.
25. Honjoh S, Yamamoto T, Uno M, Nishida E, (2009) Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C. elegans. Nature 457: 726-730.
26. Bauer J, Antoch M, Chang C, Schorl C, Kolli S, et al. (2010) Comparative transcriptional profiling identifies takeout as a gene that regulates life span. Aging (Albany NY) 2: 298-310.
27. Zid BM, Rogers AN, Katewa SD, Vargas MA, Kolipinski MC, et al. (2009) 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila. Cell 139: 149-160.
28. Shmookler Reis RJ, Xu L, Lee H, Chae M, Thaden JJ, et al. (2011) Modulation of lipid biosynthesis contributes to stress resistance and longevity of C. elegans mutants. Aging (Albany NY) 3: 125-147.
29. Hansen M, Hsu AL, Dillin A, Kenyon C, (2005) New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen. PLoS Genet 1: e17. doi:10.1371/journal.pgen.0010017.
30. Steinkraus KA, Smith ED, Davis C, Carr D, Pendergrass WR, et al. (2008) Dietary restriction suppresses proteotoxicity and enhances longevity by an hsf-1-dependent mechanism in Caenorhabditis elegans. Aging Cell 7: 394-404.
31. Smith ED, Tsuchiya M, Fox LA, Dang N, Hu D, et al. (2008) Quantitative evidence for conserved longevity pathways between divergent eukaryotic species. Genome Res 18: 564-570.
32. Balaji S, Babu MM, Iyer LM, Luscombe NM, Aravind L, (2006) Comprehensive analysis of combinatorial regulation using the transcriptional regulatory network of yeast. J Mol Biol 360: 213-227.
33. Abdulrehman D, Monteiro PT, Teixeira MC, Mira NP, Lourenco AB, et al. (2011) YEASTRACT: providing a programmatic access to curated transcriptional regulatory associations in Saccharomyces cerevisiae through a web services interface. Nucleic Acids Res 39: D136-140.
34. Lee YL, Lee CK, (2008) Transcriptional response according to strength of calorie restriction in Saccharomyces cerevisiae. Mol Cells 26: 299-307.
35. Eisenberg T, Knauer H, Schauer A, Buttner S, Ruckenstuhl C, et al. (2009) Induction of autophagy by spermidine promotes longevity. Nat Cell Biol 11: 1305-1314.
36. Chattopadhyay MK, Chen W, Poy G, Cam M, Stiles D, et al. (2009) Microarray studies on the genes responsive to the addition of spermidine or spermine to a Saccharomyces cerevisiae spermidine synthase mutant. Yeast 26: 531-544.
37. Warsow G, Greber B, Falk SS, Harder C, Siatkowski M, et al. (2010) ExprEssence- Revealing the essence of differential experimental data in the context of an interaction/regulation network. BMC Syst Biol 4: 164.
38. Steffen KK, MacKay VL, Kerr EO, Tsuchiya M, Hu D, et al. (2008) Yeast life span extension by depletion of 60s ribosomal subunits is mediated by Gcn4. Cell 133: 292-302.
39. Hansen M, Taubert S, Crawford D, Libina N, Lee SJ, et al. (2007) Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell 6: 95-110.
40. Kapahi P, Zid BM, Harper T, Koslover D, Sapin V, et al. (2004) Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol 14: 885-890.
41. Selman C, Tullet JM, Wieser D, Irvine E, Lingard SJ, et al. (2009) Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science 326: 140-144.
42. Shanley DP, Kirkwood TB, (2000) Calorie restriction and aging: a life-history analysis. Evolution 54: 740-750.
43. Fraser HB, Hirsh AE, Steinmetz LM, Scharfe C, Feldman MW, (2002) Evolutionary rate in the protein interaction network. Science 296: 750-752.
44. Eisenberg E, Levanon EY, (2003) Preferential attachment in the protein network evolution. Phys Rev Lett 91: 138701.
45. Saeed R, Deane CM, (2006) Protein protein interactions, evolutionary rate, abundance and age. BMC Bioinformatics 7: 128.
46. Kim SK, (2007) Common aging pathways in worms, flies, mice and humans. J Exp Biol 210: 1607-1612.
47. Umebayashi K, Nakano A, (2003) Ergosterol is required for targeting of tryptophan permease to the yeast plasma membrane. J Cell Biol 161: 1117-1131.
48. Carrano AC, Liu Z, Dillin A, Hunter T, (2009) A conserved ubiquitination pathway determines longevity in response to diet restriction. Nature 460: 396-399.
49. Nikko E, Pelham HR, (2009) Arrestin-mediated endocytosis of yeast plasma membrane transporters. Traffic 10: 1856-1867.
50. Babst M, (2011) MVB vesicle formation: ESCRT-dependent, ESCRT-independent and everything in between. Curr Opin Cell Biol 23: 452-457.
51. Fabrizio P, Hoon S, Shamalnasab M, Galbani A, Wei M, et al. (2010) Genome-Wide Screen in Saccharomyces cerevisiae Identifies Vacuolar Protein Sorting, Autophagy, Biosynthetic, and tRNA Methylation Genes Involved in Life Span Regulation. PLoS Genet 6: e1001024 doi:10.1371/journal.pgen.1001024.
52. Longo VD, Nislow C, Fabrizio P, (2010) Endosomal protein sorting and autophagy genes contribute to the regulation of yeast life span. Autophagy 6: 1227-1228.
53. Aouida M, Khodami-Pour A, Ramotar D, (2009) Novel role for the Saccharomyces cerevisiae oligopeptide transporter Opt2 in drug detoxification. Biochem Cell Biol 87: 653-661.
54. Sharma PK, Mittal N, Deswal S, Roy N, (2011) Calorie restriction up-regulates iron and copper transport genes in Saccharomyces cerevisiae. Mol Biosyst 7: 394-402.
55. Kakinuma Y, Ohsumi Y, Anraku Y, (1981) Properties of H+-translocating adenosine triphosphatase in vacuolar membranes of SAccharomyces cerevisiae. J Biol Chem 256: 10859-10863.
56. Chan TF, Carvalho J, Riles L, Zheng XF, (2000) A chemical genomics approach toward understanding the global functions of the target of rapamycin protein (TOR). Proc Natl Acad Sci U S A 97: 13227-13232.
57. Costanzo M, Baryshnikova A, Bellay J, Kim Y, Spear ED, et al. (2010) The genetic landscape of a cell. Science 327: 425-431.
58. Ito T, Chiba T, Ozawa R, Yoshida M, Hattori M, et al. (2001) A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proc Natl Acad Sci U S A 98: 4569-4574.
59. Flinn RJ, Yan Y, Goswami S, Parker PJ, Backer JM, (2010) The late endosome is essential for mTORC1 signaling. Mol Biol Cell 21: 833-841.
60. Sturgill TW, Cohen A, Diefenbacher M, Trautwein M, Martin DE, et al. (2008) TOR1 and TOR2 have distinct locations in live cells. Eukaryot Cell 7: 1819-1830.
61. Eldakak A, Rancati G, Rubinstein B, Paul P, Conaway V, et al. (2010) Asymmetrically inherited multidrug resistance transporters are recessive determinants in cellular replicative ageing. Nat Cell Biol 12: 799-805.
62. Plank M, Wuttke D, van Dam S, Clarke SA, de Magalhaes JP, (2012) A meta-analysis of caloric restriction gene expression profiles to infer common signatures and regulatory mechanisms. Mol Biosyst 8: 1339-1349.
63. Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Sinclair DA, (2003) Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature 423: 181-185.
64. Jaenisch R, Bird A, (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33 Suppl: 245-254.
65. Burdge GC, Hanson MA, Slater-Jefferies JL, Lillycrop KA, (2007) Epigenetic regulation of transcription: a mechanism for inducing variations in phenotype (fetal programming) by differences in nutrition during early life? Br J Nutr 97: 1036-1046.
66. Feser J, Tyler J, (2011) Chromatin structure as a mediator of aging. FEBS Lett 585: 2041-2048.
67. Vaquero A, Reinberg D, (2009) Calorie restriction and the exercise of chromatin. Genes Dev 23: 1849-1869.
68. Unal E, Kinde B, Amon A, (2011) Gametogenesis eliminates age-induced cellular damage and resets life span in yeast. Science 332: 1554-1557.
69. Mair W, Goymer P, Pletcher SD, Partridge L, (2003) Demography of dietary restriction and death in Drosophila. Science 301: 1731-1733.
70. Brawley JV, Ferro AJ, (1979) Polyamine biosynthesis during germination of yeast ascospores. J Bacteriol 140: 649-654.
71. Tabor CW, (1981) Mutants of Saccharomyces cerevisiae deficient in polyamine biosynthesis: studies on the regulation of ornithine decarboxylase. Med Biol 59: 272-278.
72. Jin Y, Bok JW, Guzman-de-Pena D, Keller NP, (2002) Requirement of spermidine for developmental transitions in Aspergillus nidulans. Mol Microbiol 46: 801-812.
73. Matsumoto M, Kurihara S, Kibe R, Ashida H, Benno Y, (2011) Longevity in mice is promoted by probiotic-induced suppression of colonic senescence dependent on upregulation of gut bacterial polyamine production. PLoS ONE 6: e23652 doi:10.1371/journal.pone.0023652.
74. Soda K, Dobashi Y, Kano Y, Tsujinaka S, Konishi F, (2009) Polyamine-rich food decreases age-associated pathology and mortality in aged mice. Exp Gerontol 44: 727-732.
75. Pnueli L, Edry I, Cohen M, Kassir Y, (2004) Glucose and nitrogen regulate the switch from histone deacetylation to acetylation for expression of early meiosis-specific genes in budding yeast. Mol Cell Biol 24: 5197-5208.
76. de Magalhaes JP, Costa J, Toussaint O, (2005) HAGR: the Human Ageing Genomic Resources. Nucleic Acids Res 33: D537-543.
77. Fischer S, Brunk BP, Chen F, Gao X, Harb OS, et al. (2011) Using OrthoMCL to assign proteins to OrthoMCL-DB groups or to cluster proteomes into new ortholog groups. Curr Protoc Bioinformatics Chapter 6Unit 6 12 11-19.
78. Ostlund G, Schmitt T, Forslund K, Kostler T, Messina DN, et al. (2010) InParanoid 7: new algorithms and tools for eukaryotic orthology analysis. Nucleic Acids Res 38: D196-203.
79. Koonin EV, Wolf YI, (2010) Constraints and plasticity in genome and molecular-phenome evolution. Nat Rev Genet 11: 487-498.
80. Aranda B, Achuthan P, Alam-Faruque Y, Armean I, Bridge A, et al. (2010) The IntAct molecular interaction database in 2010. Nucleic Acids Res 38: D525-531.
81. Xenarios I, Salwinski L, Duan XJ, Higney P, Kim SM, et al. (2002) DIP, the Database of Interacting Proteins: a research tool for studying cellular networks of protein interactions. Nucleic Acids Res 30: 303-305.
82. Ceol A, Chatr Aryamontri A, Licata L, Peluso D, Briganti L, et al. (2010) MINT, the molecular interaction database: 2009 update. Nucleic Acids Res 38: D532-539.
83. Isserlin R, El-Badrawi RA, Bader GD, (2011) The Biomolecular Interaction Network Database in PSI-MI 2.5. Database (Oxford) 2011: baq037.
84. Breitkreutz BJ, Stark C, Reguly T, Boucher L, Breitkreutz A, et al. (2008) The BioGRID Interaction Database: 2008 update. Nucleic Acids Res 36: D637-640.
85. Guldener U, Munsterkotter M, Oesterheld M, Pagel P, Ruepp A, et al. (2006) MPact: the MIPS protein interaction resource on yeast. Nucleic Acids Res 34: D436-441.
86. Stein LD, (2004) Using the Reactome database. Curr Protoc Bioinformatics Chapter 8Unit 8 7.
87. Keshava Prasad TS, Goel R, Kandasamy K, Keerthikumar S, Kumar S, et al. (2009) Human Protein Reference Database-2009 update. Nucleic Acids Res 37: D767-772.
88. Beuming T, Skrabanek L, Niv MY, Mukherjee P, Weinstein H, (2005) PDZBase: a protein-protein interaction database for PDZ-domains. Bioinformatics 21: 827-828.
89. Ruepp A, Waegele B, Lechner M, Brauner B, Dunger-Kaltenbach I, et al. (2010) CORUM: the comprehensive resource of mammalian protein complexes-2009. Nucleic Acids Res 38: D497-501.
90. Razick S, Magklaras G, Donaldson IM, (2008) iRefIndex: a consolidated protein interaction database with provenance. BMC Bioinformatics 9: 405.
91. Hornbeck PV, Chabra I, Kornhauser JM, Skrzypek E, Zhang B, (2004) PhosphoSite: A bioinformatics resource dedicated to physiological protein phosphorylation. Proteomics 4: 1551-1561.
92. Stark C, Su TC, Breitkreutz A, Lourenco P, Dahabieh M, et al. (2010) PhosphoGRID: a database of experimentally verified in vivo protein phosphorylation sites from the budding yeast Saccharomyces cerevisiae. Database (Oxford) 2010: bap026.
93. Brown KR, Jurisica I, (2007) Unequal evolutionary conservation of human protein interactions in interologous networks. Genome Biol 8: R95.
94. Michaut M, Kerrien S, Montecchi-Palazzi L, Chauvat F, Cassier-Chauvat C, et al. (2008) InteroPORC: automated inference of highly conserved protein interaction networks. Bioinformatics 24: 1625-1631.
95. Wiles AM, Doderer M, Ruan J, Gu TT, Ravi D, et al. (2010) Building and analyzing protein interactome networks by cross-species comparisons. BMC Syst Biol 4: 36.
96. Jayapandian M, Chapman A, Tarcea VG, Yu C, Elkiss A, et al. (2007) Michigan Molecular Interactions (MiMI): putting the jigsaw puzzle together. Nucleic Acids Res 35: D566-571.
97. Tarcea VG, Weymouth T, Ade A, Bookvich A, Gao J, et al. (2009) Michigan molecular interactions r2: from interacting proteins to pathways. Nucleic Acids Res 37: D642-646.
98. Wu J, Vallenius T, Ovaska K, Westermarck J, Makela TP, et al. (2009) Integrated network analysis platform for protein-protein interactions. Nat Methods 6: 75-77.
99. Lee I, Li Z, Marcotte EM, (2007) An improved, bias-reduced probabilistic functional gene network of baker's yeast, Saccharomyces cerevisiae. PLoS ONE 2: e988 doi:10.1371/journal.pone.0000988.
100. Lee I, Lehner B, Vavouri T, Shin J, Fraser AG, et al. (2010) Predicting genetic modifier loci using functional gene networks. Genome Res 20: 1143-1153.
101. Kim WK, Krumpelman C, Marcotte EM, (2008) Inferring mouse gene functions from genomic-scale data using a combined functional network/classification strategy. Genome Biol 9 Suppl 1: S5.
102. Ravasi T, Suzuki H, Cannistraci CV, Katayama S, Bajic VB, et al. (2010) An atlas of combinatorial transcriptional regulation in mouse and man. Cell 140: 744-752.
103. Cline MS, Smoot M, Cerami E, Kuchinsky A, Landys N, et al. (2007) Integration of biological networks and gene expression data using Cytoscape. Nat Protoc 2: 2366-2382.
104. Huang da W, Sherman BT, Tan Q, Kir J, Liu D, et al. (2007) DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists. Nucleic Acids Res 35: W169-175.
105. Cherry JM, Hong EL, Amundsen C, Balakrishnan R, Binkley G, et al. (2012) Saccharomyces Genome Database: the genomics resource of budding yeast. Nucleic Acids Res 40: D700-705.
106. Fisher RA (1932) Statistical methods for research workers. Edinburgh etc.: Oliver and Boyd. xiii p., 1 l. p.
107. Whitlock MC, (2005) Combining probability from independent tests: the weighted Z-method is superior to Fisher's approach. J Evol Biol 18: 1368-1373.
108. Wang YX, Catlett NL, Weisman LS, (1998) Vac8p, a vacuolar protein with armadillo repeats, functions in both vacuole inheritance and protein targeting from the cytoplasm to vacuole. J Cell Biol 140: 1063-1074.
109. Gebre S, Connor R, Xia Y, Jawed S, Bush JM, et al. (2012) Osh6 overexpression extends the lifespan of yeast by increasing vacuole fusion. Cell Cycle 11: 2176-2188.
110. Colomina N, Liu Y, Aldea M, Gari E, (2003) TOR regulates the subcellular localization of Ime1, a transcriptional activator of meiotic development in budding yeast. Mol Cell Biol 23: 7415-7424.
111. Balderhaar HJ, Arlt H, Ostrowicz C, Brocker C, Sundermann F, et al. (2010) The Rab GTPase Ypt7 is linked to retromer-mediated receptor recycling and fusion at the yeast late endosome. J Cell Sci 123: 4085-4094.