Fused in sarcoma (FUS) protein lacking nuclear localization signal (NLS) and major RNA binding motifs triggers proteinopathy and severe motor phenotype in transgenic mice

Journal of Biological Chemistry

Volumn 288, Issue 35, 2013, Pages 25266-25274

  Shelkovnikova, Tatyana A ^a,b   Peters, Owen M ^a   Deykin, Alexey V ^c   Connor Robson, Natalie ^a   Robinson, Hannah ^a   Ustyugov, Alexey A ^a,b   Bachurin, Sergey O ^b   Ermolkevich, Tatyana G ^c   Goldman, Igor L ^c   Sadchikova, Elena R ^c   Kovrazhkina, Elena A ^d   Skvortsova, Veronica I ^d   Ling, Shuo Chien ^e   Da Cruz, Sandrine ^e   Parone, Philippe A ^e   Buchman, Vladimir L ^a,b   Ninkina, Natalia N ^a,b  

^a CARDIFF UNIVERSITY   (United Kingdom)

^b INSTITUTE OF PHYSIOLOGICALLY ACTIVE COMPOUNDS   (Russian Federation)

^c INSTITUTE OF GENE BIOLOGY   (Russian Federation)

^d PIROGOV RUSSIAN NATIONAL RESEARCH MEDICAL UNIVERSITY   (Russian Federation)

^e LUDWIG INSTITUTE FOR CANCER RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYOTROPHIC LATERAL SCLEROSIS; FUSED IN SARCOMATA; NUCLEAR LOCALIZATION SIGNAL; PROTEIN AGGREGATION; RNA-BINDING MOTIF; TRANSGENIC MICE;

MAMMALS; NEURODEGENERATIVE DISEASES;

PROTEINS;

FUSED IN SARCOMA PROTEIN;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CLINICAL FEATURE; CONTROLLED STUDY; DISEASE COURSE; DISEASE SEVERITY; LIFESPAN; MORTALITY; MOTONEURON; MOTOR DYSFUNCTION; MOUSE; NERVE CELL LESION; NERVE FIBER; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; NUCLEAR LOCALIZATION SIGNAL; PATHOPHYSIOLOGY; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DEFECT; PROTEIN EXPRESSION; PROTEIN MOTIF; RNA BINDING; TRANSGENIC MOUSE;

AMYOTROPHIC LATERAL SCLEROSIS (LOU GEHRIG'S DISEASE); ANIMAL MODELS; MOTOR NEURON DISEASE; NEURODEGENERATION; PROTEIN AGGREGATION; PROTEINOPATHY; RNA METABOLISM; RNA-BINDING PROTEINS; TDP-43; TRANSGENIC MOUSE;

AMINO ACID MOTIFS; AMINO ACID SEQUENCE; AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; AXONS; CYTOPLASM; HUMANS; MICE; MICE, TRANSGENIC; MOTOR NEURONS; NUCLEAR LOCALIZATION SIGNALS; PHENOTYPE; RNA; RNA-BINDING PROTEIN FUS; SEQUENCE DELETION;

EID: 84883352466     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.492017     Document Type: Article

References (24)

1. Kwiatkowski, T. J., Jr., Bosco, D. A., Leclerc, A. L., Tamrazian, E., Vanderburg, C. R., Russ, C., Davis, A., Gilchrist, J., Kasarskis, E. J., Munsat, T., Valdmanis, P., Rouleau, G. A., Hosler, B. A., Cortelli, P., de Jong, P. J., Yoshinaga, Y., Haines, J. L., Pericak-Vance, M. A., Yan, J., Ticozzi, N., Siddique, T., McKenna-Yasek, D., Sapp, P. C., Horvitz, H. R., Landers, J. E., and Brown, R. H., Jr. (2009) Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323, 1205-1208
2. Vance, C., Rogelj, B., Hortobágyi, T., De Vos, K. J., Nishimura, A. L., Sreedharan, J., Hu, X., Smith, B., Ruddy, D., Wright, P., Ganesalingam, J., Williams, K. L., Tripathi, V., Al-Saraj, S., Al-Chalabi, A., Leigh, P. N., Blair, I. P., Nicholson, G., de Belleroche, J., Gallo, J. M., Miller, C. C., and Shaw, C. E. (2009) Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323, 1208-1211
3. Deng, H. X., Zhai, H., Bigio, E. H., Yan, J., Fecto, F., Ajroud, K., Mishra, M., Ajroud-Driss, S., Heller, S., Sufit, R., Siddique, N., Mugnaini, E., and Siddique, T. (2010) FUS-immunoreactive inclusions are a common feature in sporadic and non-SOD1 familial amyotrophic lateral sclerosis. Ann. Neurol. 67, 739-748
4. Neumann, M., Rademakers, R., Roeber, S., Baker, M., Kretzschmar, H. A., and Mackenzie, I. R. (2009)Anew subtype of frontotemporal lobar degeneration with FUS pathology. Brain 132, 2922-2931
5. Neumann, M., Roeber, S., Kretzschmar, H. A., Rademakers, R., Baker, M., and Mackenzie, I. R. (2009) Abundant FUS-immunoreactive pathology in neuronal intermediate filament inclusion disease. Acta Neuropathol. 118, 605-616
6. Munoz, D. G., Neumann, M., Kusaka, H., Yokota, O., Ishihara, K., Terada, S., Kuroda, S., and Mackenzie, I. R. (2009) FUS pathology in basophilic inclusion body disease. Acta Neuropathol. 118, 617-627
7. Cohen, N. R., Hammans, S. R., Macpherson, J., and Nicoll, J. A. (2011) New neuropathological findings in Unverricht-Lundborg disease: neuronal intranuclear and cytoplasmic inclusions. Acta Neuropathol. 121, 421-427
8. Lagier-Tourenne, C., Polymenidou, M., Hutt, K. R., Vu, A. Q., Baughn, M., Huelga, S. C., Clutario, K. M., Ling, S. C., Liang, T. Y., Mazur, C., Wancewicz, E., Kim, A. S., Watt, A., Freier, S., Hicks, G. G., Donohue, J. P., Shiue, L., Bennett, C. F., Ravits, J., Cleveland, D. W., and Yeo, G. W. (2012) Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs. Nat. Neurosci. 15, 1488-1497
9. Chen, Y., Yang, M., Deng, J., Chen, X., Ye, Y., Zhu, L., Liu, J., Ye, H., Shen, Y., Li, Y., Rao, E. J., Fushimi, K., Zhou, X., Bigio, E. H., Mesulam, M., Xu, Q., and Wu, J. Y. (2011) Expression of human FUS protein in Drosophila leads to progressive neurodegeneration. Protein Cell 2, 477-486
10. Xia, R., Liu, Y., Yang, L., Gal, J., Zhu, H., and Jia, J. (2012) Motor neuron apoptosis and neuromuscular junction perturbation are prominent features in a Drosophila model of Fus-mediated ALS. Mol. Neurodegener. 7, 10
11. Murakami, T., Yang, S. P., Xie, L., Kawano, T., Fu, D., Mukai, A., Bohm, C., Chen, F., Robertson, J., Suzuki, H., Tartaglia, G. G., Vendruscolo, M., Kaminski Schierle, G. S., Chan, F. T., Moloney, A., Crowther, D., Kaminski, C. F., Zhen, M., and St George-Hyslop, P. (2012) ALS mutations in FUS cause neuronal dysfunction and death in Caenorhabditis elegans by a dominant gain-of-function mechanism. Hum. Mol. Genet. 21, 1-9
12. Huang, C., Zhou, H., Tong, J., Chen, H., Liu, Y. J., Wang, D., Wei, X., and Xia, X. G. (2011) FUS transgenic rats develop the phenotypes of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. PLoS Genet. 7, e1002011
13. Cushman, M., Johnson, B. S., King, O. D., Gitler, A. D., and Shorter, J. (2010) Prion-like disorders: blurring the divide between transmissibility and infectivity. J. Cell Sci. 123, 1191-1201
14. Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., Bruce, J., Schuck, T., Grossman, M., Clark, C. M., McCluskey, L. F., Miller, B. L., Masliah, E., Mackenzie, I. R., Feldman, H., Feiden, W., Kretzschmar, H. A., Trojanowski, J. Q., and Lee, V. M. (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130-133
15. Ninkina, N., Peters, O., Millership, S., Salem, H., van der Putten, H., and Buchman, V. L. (2009) γ-Synucleinopathy: neurodegeneration associated with overexpression of the mouse protein. Hum. Mol. Genet. 18, 1779-1794
16. Ninkina, N., Papachroni, K., Robertson, D. C., Schmidt, O., Delaney, L., O'Neill, F., Court, F., Rosenthal, A., Fleetwood-Walker, S. M., Davies, A. M., and Buchman, V. L. (2003) Neurons expressing the highest levels of γ-synuclein are unaffected by targeted inactivation of the gene. Mol. Cell. Biol. 23, 8233-8245
17. Peters, O. M., Millership, S., Shelkovnikova, T. A., Soto, I., Keeling, L., Hann, A., Marsh-Armstrong, N., Buchman, V. L., and Ninkina, N. (2012) Selective pattern of motor system damage in γ-synuclein transgenic mice mirrors the respective pathology in amyotrophic lateral sclerosis. Neurobiol. Dis. 48, 124-131
18. Zhang, Z. C., and Chook, Y. M. (2012) Structural and energetic basis of ALS-causing mutations in the atypical proline-tyrosine nuclear localization signal of the Fused in Sarcoma protein (FUS). Proc. Natl. Acad. Sci. U.S.A. 109, 12017-12021
19. Conway, K. A., Lee, S. J., Rochet, J. C., Ding, T. T., Harper, J. D., Williamson, R. E., and Lansbury, P. T., Jr. (2000) Accelerated oligomerization by Parkinson's disease linked α-synuclein mutants. Ann. N.Y. Acad. Sci. 920, 42-45
20. Pan, K. M., Baldwin, M., Nguyen, J., Gasset, M., Serban, A., Groth, D., Mehlhorn, I., Huang, Z., Fletterick, R. J., Cohen, F. E., et al. (1993) Conversion of α-helices into β-sheets features in the formation of the scrapie prion proteins. Proc. Natl. Acad. Sci. U.S.A. 90, 10962-10966
21. Lashley, T., Rohrer, J. D., Bandopadhyay, R., Fry, C., Ahmed, Z., Isaacs, A. M., Brelstaff, J. H., Borroni, B., Warren, J. D., Troakes, C., King, A., Al-Saraj, S., Newcombe, J., Quinn, N., Ostergaard, K., Schrøder, H. D., Bojsen-Møller, M., Braendgaard, H., Fox, N. C., Rossor, M. N., Lees, A. J., Holton, J. L., and Revesz, T. (2011) A comparative clinical, pathological, biochemical, and genetic study of fused in sarcoma proteinopathies. Brain 134, 2548-2564
22. Miguel, L., Avequin, T., Delarue, M., Feuillette, S., Frébourg, T., Campion, D., and Lecourtois, M. (2012) Accumulation of insoluble forms of FUS protein correlates with toxicity in Drosophila. Neurobiol. Aging 33, 1008.e1-15
23. Mitchell, J. C., McGoldrick, P., Vance, C., Hortobagyi, T., Sreedharan, J., Rogelj, B., Tudor, E. L., Smith, B. N., Klasen, C., Miller, C. C., Cooper, J. D., Greensmith, L., and Shaw, C. E. (2013) Overexpression of human wildtype FUS causes progressive motor neuron degeneration in an age- and dose-dependent fashion. Acta Neuropathol. 125, 273-288
24. Verbeeck, C., Deng, Q., Dejesus-Hernandez, M., Taylor, G., Ceballos-Diaz, C., Kocerha, J., Golde, T., Das, P., Rademakers, R., Dickson, D. W., and Kukar, T. (2012) Expression of Fused in sarcoma mutations in mice recapitulates the neuropathology of FUS proteinopathies and provides insight into disease pathogenesis. Mol. Neurodegener. 7, 53