Live cell imaging and biophotonic methods reveal two types of mutant huntingtin inclusions

Human Molecular Genetics

Volumn 23, Issue 9, 2014, Pages 2324-2338

  Caron, Nicholas S ^a   Hung, Claudia L ^a   Atwal, Randy S ^b   Truant, Ray ^a  

^a MCMASTER UNIVERSITY   (Canada)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; HUNTINGTIN; SERINE; HUNTINGTON PROTEIN, MOUSE; NERVE PROTEIN; NUCLEAR PROTEIN;

ARTICLE; CELL INCLUSION; FLUORESCENCE IMAGING; FLUORESCENCE RECOVERY AFTER PHOTOBLEACHING; FLUORESCENCE RESONANCE ENERGY TRANSFER; MICROTUBULE; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN PHOSPHORYLATION; SINGLE CELL ANALYSIS; ANIMAL; HUNTINGTON CHOREA; METABOLISM; MOUSE; PHOSPHORYLATION; TISSUE CULTURE TECHNIQUE;

ANIMALS; FLUORESCENCE RECOVERY AFTER PHOTOBLEACHING; FLUORESCENCE RESONANCE ENERGY TRANSFER; HUNTINGTON DISEASE; INCLUSION BODIES; MICE; NERVE TISSUE PROTEINS; NUCLEAR PROTEINS; PHOSPHORYLATION; TISSUE CULTURE TECHNIQUES;

EID: 84897554245     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddt625     Document Type: Article

References (65)

1. The Huntington's Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell, 72, 971-983.
2. Duyao, M., Ambrose, C., Myers, R., Novelletto, A., Persichetti, F., Frontali, M., Folstein, S., Ross, C., Franz, M., Abbott, M. et al. (1993) Trinucleotide repeat length instability and age of onset in Huntington's disease. Nat. Genet., 4, 387-392.
3. Stine, O.C., Pleasant, N., Franz, M.L., Abbott, M.H., Folstein, S.E. and Ross, C.A. (1993) Correlation between the onset age of Huntington's disease and length of the trinucleotide repeat in IT-15. Hum. Mol. Genet., 2, 1547-1549.
4. Block-Galarza, J., Chase, K.O., Sapp, E., Vaughn, K.T., Vallee, R.B., DiFiglia, M. and Aronin, N. (1997) Fast transport and retrograde movement of huntingtin and HAP 1 in axons. Neuroreport, 8, 2247-2251.
5. Caviston, J.P., Ross, J.L., Antony, S.M., Tokito, M. and Holzbaur, E.L. (2007) Huntingtin facilitates dynein/dynactin-mediated vesicle transport. Proc. Natl. Acad. Sci. USA, 104, 10045-10050.
6. Gauthier, L.R., Charrin, B.C., Borrell-Pages, M., Dompierre, J.P., Rangone, H., Cordelieres, F.P., De Mey, J., MacDonald, M.E., Lessmann, V., Humbert, S. et al. (2004) Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell, 118, 127-138.
7. Li, S.H., Cheng, A.L., Zhou, H., Lam, S., Rao, M., Li, H. and Li, X.J. (2002) Interaction of Huntington disease protein with transcriptional activator Sp1. Mol. Cell. Biol., 22, 1277-1287.
8. Sugars, K.L. and Rubinsztein, D.C. (2003) Transcriptional abnormalities in Huntington disease. Trends Genet., 19, 233-238.
9. Zuccato, C., Ciammola, A., Rigamonti, D., Leavitt, B.R., Goffredo, D., Conti, L., MacDonald, M.E., Friedlander, R.M., Silani, V., Hayden, M.R. et al. (2001) Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease. Science, 293, 493-498.
10. Zuccato, C., Tartari, M., Crotti, A., Goffredo, D., Valenza, M., Conti, L., Cataudella, T., Leavitt, B.R., Hayden, M.R., Timmusk, T. et al. (2003) Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat. Genet., 35, 76-83.
11. DiProspero, N.A., Chen, E.Y., Charles, V., Plomann, M., Kordower, J.H. and Tagle, D.A. (2004) Early changes in Huntington's disease patient brains involve alterations in cytoskeletal and synaptic elements. J. Neurocytol., 33, 517-533.
12. Munsie, L., Caron, N., Atwal, R.S., Marsden, I., Wild, E.J., Bamburg, J.R., Tabrizi, S.J. and Truant, R. (2011) Mutant huntingtin causes defective actin remodeling during stress: defining a new role for transglutaminase 2 in neurodegenerative disease. Hum. Mol. Genet., 20, 1937-1951.
13. Shirasaki, D.I., Greiner, E.R., Al-Ramahi, I., Gray, M., Boontheung, P., Geschwind, D.H., Botas, J., Coppola, G., Horvath, S., Loo, J.A. et al. (2012) Network organization of the huntingtin proteomic interactome in mammalian brain. Neuron, 75, 41-57.
14. DiFiglia, M., Sapp, E., Chase, K.O., Davies, S.W., Bates, G.P., Vonsattel, J.P. and Aronin, N. (1997) Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science, 277, 1990-1993.
15. Mangiarini, L., Sathasivam, K., Seller, M., Cozens, B., Harper, A., Hetherington, C., Lawton, M., Trottier, Y., Lehrach, H., Davies, S.W. et al. (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell, 87, 493-506.
16. Davies, S.W., Turmaine, M., Cozens, B.A., DiFiglia, M., Sharp, A.H., Ross, C.A., Scherzinger, E., Wanker, E.E., Mangiarini, L. and Bates, G.P. (1997) Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell, 90, 537-548.
17. Goldberg, Y.P., Nicholson, D.W., Rasper, D.M., Kalchman, M.A., Koide, H.B., Graham, R.K., Bromm, M., Kazemi-Esfarjani, P., Thornberry, N.A., Vaillancourt, J.P. et al. (1996) Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nat. Genet., 13, 442-449.
18. Kim, Y.J., Yi, Y., Sapp, E., Wang, Y., Cuiffo, B., Kegel, K.B., Qin, Z.H., Aronin, N. and DiFiglia, M. (2001) Caspase 3-cleaved N-terminal fragments of wild-type and mutant huntingtin are present in normal and Huntington's disease brains, associate with membranes, and undergo calpain-dependent proteolysis. Proc. Natl. Acad. Sci. USA, 98, 12784-12789.
19. Wellington, C.L., Ellerby, L.M., Hackam, A.S., Margolis, R.L., Trifiro, M.A., Singaraja, R., McCutcheon, K., Salvesen, G.S., Propp, S.S., Bromm, M. et al. (1998) Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. J. Biol. Chem., 273, 9158-9167.
20. Wellington, C.L., Ellerby, L.M., Gutekunst, C.A., Rogers, D., Warby, S., Graham, R.K., Loubser, O., van Raamsdonk, J., Singaraja, R., Yang, Y.Z. et al. (2002) Caspase cleavage of mutant huntingtin precedes neurodegeneration in Huntington's disease. J. Neurosci., 22, 7862-7872.
21. Hoffner, G., Island, M.L. and Djian, P. (2005) Purification of neuronal inclusions of patients with Huntington's disease reveals a broad range of N-terminal fragments of expanded huntingtin and insoluble polymers. J. Neurochem., 95, 125-136.
22. Landles, C., Sathasivam, K., Weiss, A., Woodman, B., Moffitt, H., Finkbeiner, S., Sun, B., Gafni, J., Ellerby, L.M., Trottier, Y. et al. (2010) Proteolysis of mutant huntingtin produces an exon 1 fragment that accumulates as an aggregated protein in neuronal nuclei in Huntington disease. J. Biol. Chem., 285, 8808-8823.
23. Sathasivam, K., Neueder, A., Gipson, T.A., Landles, C., Benjamin, A.C., Bondulich, M.K., Smith, D.L., Faull, R.L., Roos, R.A., Howland, D. et al. (2013) Aberrant splicing of HTT generates the pathogenic exon 1 protein in Huntington disease. Proc. Natl. Acad. Sci. USA, 110, 2366-2370.
24. Ross, C.A. and Poirier, M.A. (2004) Protein aggregation and neurodegenerative disease. Nat. Med., 10(Suppl), S10-S17.
25. Hardy, J.A. and Higgins, G.A. (1992) Alzheimer's disease: the amyloid cascade hypothesis. Science, 256, 184-185.
26. Hardy, J. and Allsop, D. (1991)Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol. Sci., 12, 383-388.
27. Glabe, C.G. (2006) Common mechanisms of amyloid oligomer pathogenesis in degenerative disease. Neurobiol. Aging, 27, 570-575.
28. Cooper, J.K., Schilling, G., Peters, M.F., Herring, W.J., Sharp, A.H., Kaminsky, Z., Masone, J., Khan, F.A., Delanoy, M., Borchelt, D.R. et al. (1998) Truncated N-terminal fragments of huntingtin with expanded glutamine repeats form nuclear and cytoplasmic aggregates in cell culture. Hum. Mol. Genet., 7, 783-790.
29. Hackam, A.S., Singaraja, R., Wellington, C.L., Metzler, M., McCutcheon, K., Zhang, T., Kalchman, M. and Hayden, M.R. (1998) The influence of huntingtin protein size on nuclear localization and cellular toxicity. J. Cell Biol., 141, 1097-1105.
30. Preisinger, E., Jordan, B.M., Kazantsev, A. and Housman, D. (1999) Evidence for a recruitment and sequestration mechanism in Huntington's disease. Philos. Trans. R. Soc. London B Biol. Sci., 354, 1029-1034.
31. Gunawardena, S., Her, L.S., Brusch, R.G., Laymon, R.A., Niesman, I.R., Gordesky-Gold, B., Sintasath, L., Bonini, N.M. and Goldstein, L.S. (2003) Disruption of axonal transport by loss of huntingtin or expression of pathogenic polyQ proteins in Drosophila. Neuron, 40, 25-40.
32. Bence, N.F., Sampat, R.M. and Kopito, R.R. (2001) Impairment of the ubiquitin-proteasome system by protein aggregation. Science, 292, 1552-1555.
33. Saudou, F., Finkbeiner, S., Devys, D. and Greenberg, M.E. (1998) Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell, 95, 55-66.
34. Arrasate, M., Mitra, S., Schweitzer, E.S., Segal, M.R. and Finkbeiner, S. (2004) Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature, 431, 805-810.
35. Nagai, Y., Inui, T., Popiel, H.A., Fujikake, N., Hasegawa, K., Urade, Y., Goto, Y., Naiki, H. and Toda, T. (2007)Atoxic monomeric conformer of the polyglutamine protein. Nat. Struct. Mol. Biol., 14, 332-340.
36. Chopra, V., Fox, J.H., Lieberman, G., Dorsey, K., Matson, W., Waldmeier, P., Housman, D.E., Kazantsev, A., Young, A.B. and Hersch, S. (2007) A small-molecule therapeutic lead for Huntington's disease: preclinical pharmacology and efficacy of C2-8 in the R6/2 transgenic mouse. Proc. Natl. Acad. Sci. USA, 104, 16685-16689.
37. Bodner, R.A., Housman, D.E. and Kazantsev, A.G. (2006) New directions for neurodegenerative disease therapy: using chemical compounds to boost the formation of mutant protein inclusions. Cell Cycle, 5, 1477-1480.
38. Truant, R., Atwal, R.S., Desmond, C., Munsie, L. and Tran, T. (2008) Huntington's disease: revisiting the aggregation hypothesis in polyglutamine neurodegenerative diseases. FEBS J., 275, 4252-4262.
39. Truant, R., Raymond, L.A., Xia, J., Pinchev, D., Burtnik, A. and Atwal, R.S. (2006) Canadian Association of Neurosciences Review: polyglutamine expansion neurodegenerative diseases. Can. J. Neurol. Sci., 33, 278-291.
40. Duennwald, M.L., Jagadish, S., Muchowski, P.J. and Lindquist, S. (2006) Flanking sequences profoundly alter polyglutamine toxicity in yeast. Proc. Natl. Acad. Sci. USA, 103, 11045-11050.
41. Caron, N.S., Desmond, C.R., Xia, J. and Truant, R. (2013) Polyglutamine domain flexibility mediates the proximity between flanking sequences in huntingtin. Proc. Natl. Acad. Sci. USA, 110, 14610-14615.
42. Atwal, R.S., Xia, J., Pinchev, D., Taylor, J., Epand, R.M. and Truant, R. (2007) Huntingtin has a membrane association signal that can modulate huntingtin aggregation, nuclear entry and toxicity. Hum. Mol. Genet., 16, 2600-2615.
43. Rockabrand, E., Slepko, N., Pantalone, A., Nukala, V.N., Kazantsev, A., Marsh, J.L., Sullivan, P.G., Steffan, J.S., Sensi, S.L. and Thompson, L.M. (2007) The first 17 amino acids of Huntingtin modulate its sub-cellular localization, aggregation and effects on calcium homeostasis. Hum. Mol. Genet., 16, 61-77.
44. Atwal, R.S., Desmond, C.R., Caron, N., Maiuri, T., Xia, J., Sipione, S. and Truant, R. (2011) Kinase inhibitors modulate huntingtin cell localization and toxicity. Nat. Chem. Biol., 7, 453-460.
45. Gu, X., Greiner, E.R., Mishra, R., Kodali, R., Osmand, A., Finkbeiner, S., Steffan, J.S., Thompson, L.M., Wetzel, R. and Yang, X.W. (2009) Serines 13 and 16 are critical determinants of full-length human mutant huntingtin induced disease pathogenesis in HD mice. Neuron, 64, 828-840.
46. Di Pardo, A., Maglione, V., Alpaugh, M., Horkey, M., Atwal, R.S., Sassone, J., Ciammola, A., Steffan, J.S., Fouad, K., Truant, R. et al. (2012) Ganglioside GM1 induces phosphorylation of mutant huntingtin and restores normal motor behavior in Huntington disease mice. Proc. Natl. Acad. Sci. USA, 109, 3528-3533.
47. Burnett, B.G., Andrews, J., Ranganathan, S., Fischbeck, K.H. and Di Prospero, N.A. (2008) Expression of expanded polyglutamine targets profilin for degradation and alters actin dynamics. Neurobiol. Dis., 30, 365-374.
48. Modregger, J., DiProspero, N.A., Charles, V., Tagle, D.A. and Plomann, M. (2002) PACSIN 1 interacts with huntingtin and is absent from synaptic varicosities in presymptomatic Huntington's disease brains. Hum. Mol. Genet., 11, 2547-2558.
49. Caron, N.S., Munsie, L.N., Keillor, J.W. and Truant, R. (2012) Using FLIM-FRET to measure conformational changes of transglutaminase type 2 in live cells. PloS ONE, 7, e44159.
50. Van Der Meer, B.W., Coker, I. and Chen, S.Y.S. (1994) Resonance Energy Transfer: Theory and Data. VCH, New York.
51. Gustafsson, M.G. (2000) Surpassing the lateral resolution limit by a factor of two using structured illumination microscopy. J. Microsc., 198, 82-87.
52. Groenning, M. (2010) Binding mode of Thioflavin T and other molecular probes in the context of amyloid fibrils-current status. J. Chem. Biol., 3, 1-18.
53. Rizzo, M.A., Springer, G.H., Granada, B. and Piston, D.W. (2004) An improvedcyan fluorescent protein variant useful forFRET. Nat. Biotechnol., 22, 445-449.
54. Rizzo, M.A., Springer, G., Segawa, K., Zipfel, W.R. and Piston, D.W.(2006) Optimization of pairings and detection conditions for measurement ofFRET between cyan and yellow fluorescent proteins. Microsc. Microanal., 12, 238-254.
55. Chen, Y., Mills, J.D. and Periasamy, A. (2003) Protein localization in living cells and tissues using FRET and FLIM. Differentiation, 71, 528-541.
56. Wallrabe, H. and Periasamy, A. (2005) Imaging protein molecules using FRET and FLIM microscopy. Curr. Opin. Biotechnol., 16, 19-27.
57. Tsien, R.Y., Bacskai, B.J. and Adams, S.R. (1993) FRET for studying intracellular signalling. Trends Cell Biol., 3, 242-245.
58. Meyvis, T.K., De Smedt, S.C., Van Oostveldt, P. and Demeester, J. (1999) Fluorescence recovery after photobleaching: a versatile tool for mobility and interaction measurements in pharmaceutical research. Pharm. Res., 16, 1153-1162.
59. Howell, J.L. and Truant, R. (2002) Live-cell nucleocytoplasmic protein shuttle assay utilizing laser confocal microscopy and FRAP. BioTechniques, 32, 80-82, 84, 86-87.
60. Goedhart, J., von Stetten, D., Noirclerc-Savoye, M., Lelimousin, M., Joosen, L., Hink, M.A., van Weeren, L., Gadella, T.W. Jr. and Royant, A. (2012) Structure-guided evolution of cyan fluorescent proteins towards a quantum yield of 93%. Nat. Commun., 3, 751.
61. Scherzinger, E., Lurz, R., Turmaine, M., Mangiarini, L., Hollenbach, B., Hasenbank, R., Bates, G.P., Davies, S.W., Lehrach, H. and Wanker, E.E. (1997) Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell, 90, 549-558.
62. Poirier, M.A., Li, H., Macosko, J., Cai, S., Amzel, M. and Ross, C.A. (2002) Huntingtin spheroids and protofibrils as precursors in polyglutamine fibrilization. J. Biol. Chem., 277, 41032-41037.
63. Waelter, S., Boeddrich, A., Lurz, R., Scherzinger, E., Lueder, G., Lehrach, H. and Wanker, E.E. (2001)Accumulation of mutant huntingtin fragments in aggresome-like inclusion bodies as a result of insufficient protein degradation. Mol. Biol. Cell, 12, 1393-1407.
64. Chai, Y., Shao, J., Miller, V.M., Williams, A. and Paulson, H.L. (2002) Live-cell imaging reveals divergent intracellulardynamics of polyglutamine disease proteins and supports a sequestration model of pathogenesis. Proc. Natl. Acad. Sci. USA, 99, 9310-9315.
65. Hoffner, G., Kahlem, P. and Djian, P. (2002) Perinuclear localization of huntingtin as a consequence of its binding to microtubules through an interaction with beta-tubulin: relevance to Huntington's disease. J. Cell Sci., 115, 941-948.