VAPB/ALS8 MSP Ligands Regulate Striated Muscle Energy Metabolism Critical for Adult Survival in

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Mutations in VAPB/ALS8 are associated with amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), two motor neuron diseases that often include alterations in energy metabolism. We have shown that C. elegans and Drosophila neurons secrete a cleavage product of VAPB, the N-terminal major sperm protein domain (vMSP). Secreted vMSPs signal through Roundabout and Lar-like receptors expressed on striated muscle. The muscle signaling pathway localizes mitochondria to myofilaments, alters their fission/fusion balance, and promotes energy production. Here, we show that neuronal loss of the C. elegans VAPB homolog triggers metabolic alterations that appear to compensate for muscle mitochondrial dysfunction. When vMSP levels drop, cytoskeletal or mitochondrial abnormalities in muscle induce elevated DAF-16, the Forkhead Box O (FoxO) homolog, transcription factor activity. DAF-16 promotes muscle triacylglycerol accumulation, increases ATP levels in adults, and extends lifespan, despite reduced muscle mitochondria electron transport chain activity. Finally, Vapb knock-out mice exhibit abnormal muscular triacylglycerol levels and FoxO target gene transcriptional responses to fasting and refeeding. Our data indicate that impaired vMSP signaling to striated muscle alters FoxO activity, which affects energy metabolism. Abnormalities in energy metabolism of ALS patients may thus constitute a compensatory mechanism counterbalancing skeletal muscle mitochondrial dysfunction.

Vyšlo v časopise: VAPB/ALS8 MSP Ligands Regulate Striated Muscle Energy Metabolism Critical for Adult Survival in. PLoS Genet 9(9): e32767. doi:10.1371/journal.pgen.1003738
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003738

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1. KiernanMC, VucicS, CheahBC, TurnerMR, EisenA, et al. (2011) Amyotrophic lateral sclerosis. Lancet 377 : 942–955.

2. NishimuraAL, Mitne-NetoM, SilvaHC, Richieri-CostaA, MiddletonS, et al. (2004) A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am J Hum Genet 75 : 822–831.

3. ChenHJ, AnagnostouG, ChaiA, WithersJ, MorrisA, et al. (2010) Characterization of the properties of a novel mutation in VAPB in familial amyotrophic lateral sclerosis. J Biol Chem 285 : 40266–40281.

4. KabashiE, El OussiniH, BercierV, Gros-LouisF, ValdmanisPN, et al. (2013) Investigating the contribution of VAPB/ALS8 loss of function in amyotrophic lateral sclerosis. Hum Mol Genet 22 : 2350–2360.

5. AnagnostouG, AkbarMT, PaulP, AngelinettaC, SteinerTJ, et al. (2010) Vesicle associated membrane protein B (VAPB) is decreased in ALS spinal cord. Neurobiol Aging 31 : 969–985.

6. TeulingE, AhmedS, HaasdijkE, DemmersJ, SteinmetzMO, et al. (2007) Motor neuron disease-associated mutant vesicle-associated membrane protein-associated protein (VAP) B recruits wild-type VAPs into endoplasmic reticulum-derived tubular aggregates. J Neurosci 27 : 9801–9815.

7. Mitne-NetoM, Machado-CostaM, MarchettoMC, BengtsonMH, JoazeiroCA, et al. (2011) Downregulation of VAPB expression in motor neurons derived from induced pluripotent stem cells of ALS8 patients. Hum Mol Genet 20 : 3642–3652.

8. LoewenCJ, LevineTP (2005) A highly conserved binding site in vesicle-associated membrane protein-associated protein (VAP) for the FFAT motif of lipid-binding proteins. J Biol Chem 280 : 14097–14104.

9. AmarilioR, RamachandranS, SabanayH, LevS (2005) Differential regulation of endoplasmic reticulum structure through VAP-Nir protein interaction. J Biol Chem 280 : 5934–5944.

10. LevS, Ben HalevyD, PerettiD, DahanN (2008) The VAP protein family: from cellular functions to motor neuron disease. Trends Cell Biol 18 : 282–290.

11. PerettiD, DahanN, ShimoniE, HirschbergK, LevS (2008) Coordinated lipid transfer between the endoplasmic reticulum and the Golgi complex requires the VAP proteins and is essential for Golgi-mediated transport. Mol Biol Cell 19 : 3871–3884.

12. De VosKJ, MorotzGM, StoicaR, TudorEL, LauKF, et al. (2012) VAPB interacts with the mitochondrial protein PTPIP51 to regulate calcium homeostasis. Hum Mol Genet 21 : 1299–1311.

13. TsudaH, HanSM, YangY, TongC, LinYQ, et al. (2008) The amyotrophic lateral sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors. Cell 133 : 963–977.

14. HanSM, CotteePA, MillerMA (2010) Sperm and oocyte communication mechanisms controlling C. elegans fertility. Dev Dyn 239 : 1265–1281.

15. HanSM, TsudaH, YangY, VibbertJ, CotteeP, et al. (2012) Secreted VAPB/ALS8 Major Sperm Protein Domains Modulate Mitochondrial Localization and Morphology via Growth Cone Guidance Receptors. Dev Cell 22 : 348–362.

16. MarquesVD, BarreiraAA, DavisMB, Abou-SleimanPM, SilvaWAJr, et al. (2006) Expanding the phenotypes of the Pro56Ser VAPB mutation: proximal SMA with dysautonomia. Muscle Nerve 34 : 731–739.

17. DupuisL, PradatPF, LudolphAC, LoefflerJP (2011) Energy metabolism in amyotrophic lateral sclerosis. Lancet Neurol 10 : 75–82.

18. GalloV, WarkPA, JenabM, PearceN, BrayneC, et al. (2013) Prediagnostic body fat and risk of death from amyotrophic lateral sclerosis: The EPIC cohort. Neurology 80 : 829–838.

19. DupuisL, CorciaP, FerganiA, Gonzalez De AguilarJL, Bonnefont-RousselotD, et al. (2008) Dyslipidemia is a protective factor in amyotrophic lateral sclerosis. Neurology 70 : 1004–1009.

20. DorstJ, KuhnleinP, HendrichC, KassubekJ, SperfeldAD, et al. (2011) Patients with elevated triglyceride and cholesterol serum levels have a prolonged survival in amyotrophic lateral sclerosis. J Neurol 258 : 613–617.

21. HerndonLA, SchmeissnerPJ, DudaronekJM, BrownPA, ListnerKM, et al. (2002) Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans. Nature 419 : 808–814.

22. McGeeMD, WeberD, DayN, VitelliC, CrippenD, et al. (2011) Loss of intestinal nuclei and intestinal integrity in aging C. elegans. Aging cell 10 : 699–710.

23. KubagawaHM, WattsJL, CorriganC, EdmondsJW, SztulE, et al. (2006) Oocyte signals derived from polyunsaturated fatty acids control sperm recruitment in vivo. Nat Cell Biol 8 : 1143–1148.

24. KlapperM, EhmkeM, PalgunowD, BohmeM, MatthausC, et al. (2011) Fluorescence-based fixative and vital staining of lipid droplets in Caenorhabditis elegans reveal fat stores using microscopy and flow cytometry approaches. J Lipid Res 52 : 1281–1293.

25. GrantB, HirshD (1999) Receptor-mediated endocytosis in the Caenorhabditis elegans oocyte. Mol Biol Cell 10 : 4311–4326.

26. MoumenA, VirardI, RaoulC (2011) Accumulation of wildtype and ALS-linked mutated VAPB impairs activity of the proteasome. PloS One 6: e26066.

27. GkogkasC, MiddletonS, KremerAM, WardropeC, HannahM, et al. (2008) VAPB interacts with and modulates the activity of ATF6. Hum Mol Genet 17 : 1517–1526.

28. BasseriS, AustinRC (2012) Endoplasmic reticulum stress and lipid metabolism: mechanisms and therapeutic potential. Biochem Res Int 2012 : 841362.

29. UranoF, CalfonM, YonedaT, YunC, KiralyM, et al. (2002) A survival pathway for Caenorhabditis elegans with a blocked unfolded protein response. J Cell Biol 158 : 639–646.

30. WylesJP, McMasterCR, RidgwayND (2002) VAMP-associated protein-A (VAP-A) interacts with the oxysterol binding protein (OSBP) to modify export from the endoplasmic reticulum. J Biol Chem 277 : 29908–29918.

31. JansenM, OhsakiY, Rita RegaL, BittmanR, OlkkonenVM, et al. (2011) Role of ORPs in sterol transport from plasma membrane to ER and lipid droplets in mammalian cells. Traffic 12 : 218–231.

32. PerettiD, DahanN, ShimoniE, HirschbergK, LevS (2008) Coordinated lipid transfer between the endoplasmic reticulum and the Golgi complex requires the VAP proteins and is essential for Golgi-mediated transport. Mol Biol Cell 19 : 3871–3884.

33. YochemJ, HermanRK (2003) Investigating C. elegans development through mosaic analysis. Development 130 : 4761–4768.

34. YangY, HanSM, MillerMA (2010) MSP hormonal control of the oocyte MAP kinase cascade and reactive oxygen species signaling. Dev Biol 342 : 96–107.

35. OhSW, MukhopadhyayA, DixitBL, RahaT, GreenMR, et al. (2006) Identification of direct DAF-16 targets controlling longevity, metabolism and diapause by chromatin immunoprecipitation. Nat Genet 38 : 251–257.

36. Halaschek-WienerJ, KhattraJS, McKayS, PouzyrevA, StottJM, et al. (2005) Analysis of long-lived C. elegans daf-2 mutants using serial analysis of gene expression. Genome Res 15 : 603–615.

37. MurphyCT (2006) The search for DAF-16/FOXO transcriptional targets: approaches and discoveries. Exp Gerontol 41 : 910–921.

38. MurphyCT, McCarrollSA, BargmannCI, FraserA, KamathRS, et al. (2003) Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424 : 277–283.

39. McElweeJ, BubbK, ThomasJH (2003) Transcriptional outputs of the Caenorhabditis elegans forkhead protein DAF-16. Aging Cell 2 : 111–121.

40. HendersonST, BonafeM, JohnsonTE (2006) daf-16 protects the nematode Caenorhabditis elegans during food deprivation. J Gerontol A Biol Sci Med Sci 61 : 444–460.

41. LandisJN, MurphyCT (2010) Integration of diverse inputs in the regulation of Caenorhabditis elegans DAF-16/FOXO. Dev Dyn 239 : 1405–1412.

42. WilliamsTW, DumasKJ, HuPJ (2010) EAK proteins: novel conserved regulators of C. elegans lifespan. Aging 2 : 742–747.

43. HouthoofdK, BraeckmanBP, LenaertsI, BrysK, MatthijssensF, et al. (2005) DAF-2 pathway mutations and food restriction in aging Caenorhabditis elegans differentially affect metabolism. Neurobiol Aging 26 : 689–696.

44. BraeckmanBP, HouthoofdK, De VreeseA, VanfleterenJR (2002) Assaying metabolic activity in ageing Caenorhabditis elegans. Mech Ageing Dev 123 : 105–119.

45. LinK, HsinH, LibinaN, KenyonC (2001) Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat Genet 28 : 139–145.

46. StefanCJ, ManfordAG, BairdD, Yamada-HanffJ, MaoY, et al. (2011) Osh proteins regulate phosphoinositide metabolism at ER-plasma membrane contact sites. Cell 144 : 389–401.

47. KosinskiM, McDonaldK, SchwartzJ, YamamotoI, GreensteinD (2005) C. elegans sperm bud vesicles to deliver a meiotic maturation signal to distant oocytes. Development 132 : 3357–3369.

48. DillinA, HsuAL, Arantes-OliveiraN, Lehrer-GraiwerJ, HsinH, et al. (2002) Rates of behavior and aging specified by mitochondrial function during development. Science 298 : 2398–2401.

49. LeeSS, LeeRY, FraserAG, KamathRS, AhringerJ, et al. (2003) A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity. Nat Genet 33 : 40–48.

50. BillingO, KaoG, NarediP (2011) Mitochondrial function is required for secretion of DAF-28/insulin in C. elegans. PloS One 6: e14507.

51. GreerEL, BankoMR, BrunetA (2009) AMP-activated protein kinase and FoxO transcription factors in dietary restriction-induced longevity. Ann N Y Acad Sci 1170 : 688–692.

52. BrisbinS, LiuJ, BoudreauJ, PengJ, EvangelistaM, et al. (2009) A role for C. elegans Eph RTK signaling in PTEN regulation. Dev Cell 17 : 459–469.

53. GeorgeSE, SimokatK, HardinJ, ChisholmAD (1998) The VAB-1 Eph receptor tyrosine kinase functions in neural and epithelial morphogenesis in C. elegans. Cell 92 : 633–643.

54. MillerMA, RuestPJ, KosinskiM, HanksSK, GreensteinD (2003) An Eph receptor sperm-sensing control mechanism for oocyte meiotic maturation in Caenorhabditis elegans. Genes Dev 17 : 187–200.

55. MiyataS, BegunJ, TroemelER, AusubelFM (2008) DAF-16-dependent suppression of immunity during reproduction in Caenorhabditis elegans. Genetics 178 : 903–918.

56. ChengZ, WhiteMF (2011) Targeting Forkhead box O1 from the concept to metabolic diseases: lessons from mouse models. Antioxid Redox Signal 14 : 649–661.

57. KameiY, MiuraS, SuganamiT, AkaikeF, KanaiS, et al. (2008) Regulation of SREBP1c gene expression in skeletal muscle: role of retinoid X receptor/liver X receptor and forkhead-O1 transcription factor. Endocrinology 149 : 2293–2305.

58. KameiY, OhizumiH, FujitaniY, NemotoT, TanakaT, et al. (2003) PPARgamma coactivator 1beta/ERR ligand 1 is an ERR protein ligand, whose expression induces a high-energy expenditure and antagonizes obesity. Proc Natl Acad Sci U S A 100 : 12378–12383.

59. KameiY, MiuraS, SuzukiM, KaiY, MizukamiJ, et al. (2004) Skeletal muscle FOXO1 (FKHR) transgenic mice have less skeletal muscle mass, down-regulated Type I (slow twitch/red muscle) fiber genes, and impaired glycemic control. J Biol Chem 279 : 41114–41123.

60. ReaSL, VenturaN, JohnsonTE (2007) Relationship between mitochondrial electron transport chain dysfunction, development, and life extension in Caenorhabditis elegans. PLoS Biol 5: e259.

61. HondaY, HondaS (1999) The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. FASEB J 13 : 1385–1393.

62. CrugnolaV, LampertiC, LucchiniV, RonchiD, PeverelliL, et al. (2010) Mitochondrial respiratory chain dysfunction in muscle from patients with amyotrophic lateral sclerosis. Arch Neurol 67 : 849–854.

63. ZhouJ, YiJ, FuR, LiuE, SiddiqueT, et al. (2010) Hyperactive intracellular calcium signaling associated with localized mitochondrial defects in skeletal muscle of an animal model of amyotrophic lateral sclerosis. J Biol Chem 285 : 705–712.

64. BernardiniC, CensiF, LattanziW, BarbaM, CalcagniniG, et al. (2013) Mitochondrial network genes in the skeletal muscle of amyotrophic lateral sclerosis patients. PloS One 8: e57739.

65. LegerB, VerganiL, SoraruG, HespelP, DeraveW, et al. (2006) Human skeletal muscle atrophy in amyotrophic lateral sclerosis reveals a reduction in Akt and an increase in atrogin-1. FASEB J 20 : 583–585.

66. ForrestS, ChaiA, SanhuezaM, MarescottiM, ParryK, et al. (2013) Increased levels of phosphoinositides cause neurodegeneration in a Drosophila model of amyotrophic lateral sclerosis. Hum Mol Genet 22 : 2689–2704.

67. BrennerS (1974) The genetics of Caenorhabditis elegans. Genetics 77 : 71–94.

68. KamathRS, AhringerJ (2003) Genome-wide RNAi screening in Caenorhabditis elegans. Methods 30 : 313–321.

69. BlighEG, DyerWJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37 : 911–917.

70. GilmoreK, WilsonM (1999) The use of chloromethyl-X-rosamine (Mitotracker red) to measure loss of mitochondrial membrane potential in apoptotic cells is incompatible with cell fixation. Cytometry 36 : 355–358.