A role for calpain-dependent cleavage of TDP-43 in amyotrophic lateral sclerosis pathology

Nature Communications

Volumn 3, Issue , 2012, Pages

  Yamashita, Takenari ^a,b   Hideyama, Takuto ^a,b   Hachiga, Kosuke ^b   Teramoto, Sayaka ^a,b   Takano, Jiro ^c   Iwata, Nobuhisa ^c,d   Saido, Takaomi C ^c   Kwak, Shin ^a,b,e  

^a JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

^b UNIVERSITY OF TOKYO   (Japan)

^c RIKEN BRAIN SCIENCE INSTITUTE   (Japan)

^d NAGASAKI UNIVERSITY GRADUATE SCHOOL OF BIOMEDICAL SCIENCES   (Japan)

^e INTERNATIONAL UNIVERSITY OF HEALTH AND WELFARE   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

AMPA RECEPTOR; CALPAIN; TAR DNA BINDING PROTEIN;

ENZYME ACTIVITY; GENE; MUTAGENICITY; NEUROLOGY; PATHOLOGY; PERMEABILITY; RNA; RODENT;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVATION; MOTONEURON; MOUSE; NONHUMAN; PATHOGENESIS; PROTEIN CLEAVAGE; PROTEIN LOCALIZATION; UPREGULATION;

MUS; MUS MUSCULUS;

EID: 84871734357     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms2303     Document Type: Article

References (59)

1. Gendron, T. F. & Petrucelli, L. Rodent models of TDP-43 proteinopathy: investigating the mechanisms of TDP-43-mediated neurodegeneration. J. Mol. Neurosci. 45, 486-499 (2011).
2. Fiesel, F. C. et al. Knockdown of transactive response DNA-binding protein (TDP-43) downregulates histone deacetylase 6. EMBO J. 29, 209-221 (2010).
3. Zhang, Y. J. et al. Aberrant cleavage of TDP-43 enhances aggregation and cellular toxicity. Proc. Natl Acad. Sci. USA 106, 7607-7612 (2009).
4. Nonaka, T., Kametani, F., Arai, T., Akiyama, H. & Hasegawa, M. Truncation and pathogenic mutations facilitate the formation of intracellular aggregates of TDP-43. Hum. Mol. Genet. 18, 3353-3364 (2009).
5. Daoud, H. et al. Contribution of TARDBP mutations to sporadic amyotrophic lateral sclerosis. J. Med. Genet. 46, 112-114 (2009).
6. Johnson, B. S., McCaffery, J. M., Lindquist, S. & Gitler, A. D. A yeast TDP-43 proteinopathy model: exploring the molecular determinants of TDP-43 aggregation and cellular toxicity. Proc. Natl Acad. Sci. USA 105, 6439-6444 (2008).
7. Iguchi, Y. et al. TDP-43 depletion induces neuronal cell damage through dysregulation of Rho family GTPases. J. Biol. Chem. 284, 22059-22066 (2009).
8. Arai, T. et al. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem. Biophys. Res. Commun. 351, 602-611 (2006).
9. Neumann, M. et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130-133 (2006).
10. Hasegawa, M. et al. Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Ann. Neurol. 64, 60-70 (2008).
11. Kwak, S. & Kawahara, Y. Deficient RNA editing of GluR2 and neuronal death in amyotropic lateral sclerosis. J. Mol. Med. 83, 110-120 (2005).
12. Kawahara, Y. et al. Glutamate receptors: RNA editing and death of motor neurons. Nature 427, 801 (2004).
13. Aizawa, H. et al. TDP-43 pathology in sporadic ALS occurs in motor neurons lacking the RNA editing enzyme ADAR2. Acta Neuropathol. 120, 75-84 (2010).
14. Hideyama, T. et al. Profound downregulation of the RNA editing enzyme ADAR2 in ALS spinal motor neurons. Neurobiol. Dis. 45, 1121-1128 (2012).
15. Melcher, T. et al. A mammalian RNA editing enzyme. Nature 379, 460-464 (1996).
16. Higuchi, M. et al. Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2. Nature 406, 78-81 (2000).
17. Seeburg, P. H. A-to-I editing: new and old sites, functions and speculations. Neuron 35, 17-20 (2002).
18. Hideyama, T. et al. Induced loss of ADAR2 engenders slow death of motor neurons from Q/R site-unedited GluR2. J. Neurosci. 30, 11917-11925 (2010).
19. Yamashita, T., Hideyama, T., Teramoto, S. & Kwak, S. The abnormal processing of TDP-43 is not an upstream event of reduced ADAR2 activity in ALS motor neurons. Neurosci. Res. 73, 153-160 (2012).
20. Zhang, Y. J. et al. Progranulin mediates caspase-dependent cleavage of TAR DNA binding protein-43. J. Neurosci. 27, 10530-10534 (2007).
21. Ayala, Y. M. et al. Structural determinants of the cellular localization and shuttling of TDP-43. J. Cell Sci. 121, 3778-3785 (2008).
22. Igaz, L. M. et al. Expression of TDP-43 C-terminal fragments in vitro recapitulates pathological features of TDP-43 proteinopathies. J. Biol. Chem. 284, 8516-8524 (2009).
23. Nishimoto, Y. et al. Characterization of alternative isoforms and inclusion body of the TAR DNA binding protein-43. J. Biol. Chem. 285, 608-619 (2010).
24. Tan, C. F. et al. TDP-43 immunoreactivity in neuronal inclusions in familial amyotrophic lateral sclerosis with or without SOD1 gene mutation. Acta Neuropathol. 113, 535-542 (2007).
25. Hideyama, T. & Kwak, S. When does ALS start? ADAR2-GluA2 hypothesis for the etiology of sporadic ALS. Front. Mol. Neurosci. 4, 33 (2011).
26. Kask, K. et al. The AMPA receptor subunit GluR-B in its Q/R site-unedited form is not essential for brain development and function. Proc. Natl Acad. Sci. USA 95, 13777-13782 (1998).
27. Takano, J. et al. Calpain mediates excitotoxic DNA fragmentation via mitochondrial pathways in adult brains: evidence from calpastatin mutant mice. J. Biol. Chem. 280, 16175-16184 (2005).
28. Higuchi, M. et al. Distinct mechanistic roles of calpain and caspase activation in neurodegeneration as revealed in mice overexpressing their specific inhibitors. J. Biol. Chem. 280, 15229-15237 (2005).
29. Dormann, D. et al. Proteolytic processing of TAR DNA binding protein-43 by caspases produces C-terminal fragments with disease defining properties independent of progranulin. J. Neurochem. 110, 1082-1094 (2009).
30. Chen-Plotkin, A. S., Lee, V. M. & Trojanowski, J. Q. TAR DNA-binding protein 43 in neurodegenerative disease. Nat. Rev. Neurol. 6, 211-220 (2010).
31. Lagier-Tourenne, C., Polymenidou, M. & Cleveland, D. W. TDP-43 and FUS/ TLS: emerging roles in RNA processing and neurodegeneration. Hum. Mol. Genet. 19, R46-R64 (2010).
32. Feldmeyer, D. et al. Neurological dysfunctions in mice expressing different levels of the Q/R site-unedited AMPAR subunit GluR-B. Nat. Neurosci. 2, 57-64 (1999).
33. Cushman, M., Johnson, B. S., King, O. D., Gitler, A. D. & Shorter, J. Prion-like disorders: blurring the divide between transmissibility and infectivity. J. Cell Sci. 123, 1191-1201 (2010).
34. Chen, A. K. et al. Induction of amyloid fibrils by the C-terminal fragments of TDP-43 in amyotrophic lateral sclerosis. J. Am. Chem. Soc. 132, 1186-1187 (2010).
35. Wils, H. et al. TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degeneration. Proc. Natl Acad. Sci. USA 107, 3858-3863 (2010).
36. Carriedo, S. G., Yin, H. Z. & Weiss, J. H. Motor neurons are selectively vulnerable to AMPA/kainate receptor-mediated injury in vitro. J. Neurosci. 16, 4069-4079 (1996).
37. Kawahara, Y. et al. Human spinal motoneurons express low relative abundance of GluR2 mRNA: an implication for excitotoxicity in ALS. J. Neurochem. 85, 680-689 (2003).
38. Sun, H., Kawahara, Y., Ito, K., Kanazawa, I. & Kwak, S. Expression profile of AMPA receptor subunit mRNA in single adult rat brain and spinal cord neurons in situ. Neurosci. Res. 52, 228-234 (2005).
39. Wilson, A. C., Dugger, B. N., Dickson, D. W. & Wang, D. S. TDP-43 in aging and Alzheimer's disease - a review. Int. J. Clin. Exp. Pathol. 4, 147-155 (2011).
40. McKee, A. C. et al. TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy. J. Neuropathol. Exp. Neurol. 69, 918-929 (2010).
41. Moisse, K. et al. Divergent patterns of cytosolic TDP-43 and neuronal progranulin expression following axotomy: implications for TDP-43 in the physiological response to neuronal injury. Brain Res. 1249, 202-211 (2009).
42. Kanazawa, M. et al. Biochemical and histopathological alterations in TAR DNA-binding protein-43 after acute ischemic stroke in rats. J. Neurochem. 116, 957-965 (2011).
43. Geser, F. et al. Pathological 43-kDa transactivation response DNA-binding protein in older adults with and without severe mental illness. Arch. Neurol. 67, 1238-1250 (2010).
44. Hideyama, T., Teramoto, S., Hachiga, K., Yamashita, T. & Kwak, S. Cooccurrence of TDP-43 mislocalization with reduced activity of an RNA editing enzyme, ADAR2, in aged mouse motor neurons. PLoS One 7, e43469 (2012).
45. Bezprozvanny, I. Calcium signaling and neurodegenerative diseases. Trends Mol. Med. 15, 89-100 (2009).
46. Rao, R. V., Ellerby, H. M. & Bredesen, D. E. Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ. 11, 372-380 (2004).
47. Lindholm, D., Wootz, H. & Korhonen, L. ER stress and neurodegenerative diseases. Cell Death Differ. 13, 385-392 (2006).
48. Saxena, S., Cabuy, E. & Caroni, P. A role for motoneuron subtype-selective ER stress in disease manifestations of FALS mice. Nat. Neurosci. 12, 627-636 (2009).
49. Mackenzie, I. R. et al. Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations. Ann. Neurol. 61, 427-434 (2007).
50. Stifanese, R. et al. Adaptive modifications in the calpain/calpastatin system in brain cells after persistent alteration in Ca2+ homeostasis. J. Biol. Chem. 285, 631-643 (2010).
51. Wootz, H., Hansson, I., Korhonen, L. & Lindholm, D. XIAP decreases caspase- 12 cleavage and calpain activity in spinal cord of ALS transgenic mice. Exp. Cell Res. 312, 1890-1898 (2006).
52. Wootz, H., Enjin, A., Wallen-Mackenzie, A., Lindholm, D. & Kullander, K. Reduced VGLUT2 expression increases motor neuron viability in Sod1(G93A) mice. Neurobiol. Dis. 37, 58-66 (2010).
53. Stallings, N. R., Puttaparthi, K., Luther, C. M., Burns, D. K. & Elliott, J. L. Progressive motor weakness in transgenic mice expressing human TDP-43. Neurobiol. Dis. 40, 404-414 (2010).
54. Igaz, L. M. et al. Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice. J. Clin. Invest. 121, 726-738 (2011).
55. Buratti, E. et al. TDP-43 binds heterogeneous nuclear ribonucleoprotein A/B through its C-terminal tail: an important region for the inhibition of cystic fibrosis transmembrane conductance regulator exon 9 splicing. J. Biol. Chem. 280, 37572-37584 (2005).
56. Kim, S. H., Shanware, N. P., Bowler, M. J. & Tibbetts, R. S. Amyotrophic lateral sclerosis-associated proteins TDP-43 and FUS/TLS function in a common biochemical complex to co-regulate HDAC6 mRNA. J. Biol. Chem. 285, 34097-34105 (2010).
57. Lee, M. S. et al. Neurotoxicity induces cleavage of p35 to p25 by calpain. Nature 405, 360-364 (2000).
58. Sato, K. et al. Calpastatin, an endogenous calpain-inhibitor protein, regulates the cleavage of the Cdk5 activator p35 to p25. J. Neurochem. 117, 504-515 (2011).
59. Kawahara, Y., Ito, K., Ito, M., Tsuji, S. & Kwak, S. Novel splice variants of human ADAR2 mRNA: skipping of the exon encoding the dsRNA-binding domains, and multiple C-terminal splice sites. Gene 363, 193-201 (2005).