Low molecular weight species of TDP-43 generated by abnormal splicing form inclusions in amyotrophic lateral sclerosis and result in motor neuron death

Acta Neuropathologica

Volumn 130, Issue 1, 2015, Pages 49-61

  Xiao, Shangxi ^a   Sanelli, Teresa ^a   Chiang, Helen ^a,b   Sun, Yulong ^b   Chakrabartty, Avijit ^b   Keith, Julia ^b,c   Rogaeva, Ekaterina ^a   Zinman, Lorne ^c   Robertson, Janice ^a,b  

^a UNIVERSITY OF TORONTO   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c SUNNYBROOK RESEARCH INSTITUTE   (Canada)

Author keywords

Alternative splicing; Alternative translation; Amyotrophic lateral sclerosis; C terminal species; Frontotemporal lobar degeneration; TDP 35; TDP 43

Indexed keywords

TAR DNA BINDING PROTEIN; DNA BINDING PROTEIN; TDP-43 PROTEIN, HUMAN;

ADULT; AGED; ALTERNATIVE RNA SPLICING; AMYOTROPHIC LATERAL SCLEROSIS; ARTICLE; CELL AGGREGATION; CELLULAR DISTRIBUTION; CLINICAL ARTICLE; CODON; CYTOPLASM; FEMALE; FRONTOTEMPORAL DEMENTIA; HUMAN; IMMUNOBLOTTING; MALE; MIDDLE AGED; MOLECULAR WEIGHT; MOTONEURON; NERVE CELL NECROSIS; NEUROBLASTOMA CELL; PRIORITY JOURNAL; SPINAL CORD TRANSSECTION; TRANSLATION INITIATION; UPREGULATION; AMINO ACID SEQUENCE; CELL DEATH; CELL INCLUSION; CELL NUCLEUS; GENETICS; METABOLISM; MOLECULAR GENETICS; NUCLEOTIDE SEQUENCE; PATHOLOGY; PHYSIOLOGY; SPINAL CORD; TUMOR CELL LINE; VERY ELDERLY;

AGED; AGED, 80 AND OVER; ALTERNATIVE SPLICING; AMINO ACID SEQUENCE; AMYOTROPHIC LATERAL SCLEROSIS; BASE SEQUENCE; CELL DEATH; CELL LINE, TUMOR; CELL NUCLEUS; CYTOPLASM; DNA-BINDING PROTEINS; FEMALE; FRONTOTEMPORAL LOBAR DEGENERATION; HUMANS; INCLUSION BODIES; MALE; MIDDLE AGED; MOLECULAR SEQUENCE DATA; MOLECULAR WEIGHT; MOTOR NEURONS; SPINAL CORD;

EID: 84931004098     PISSN: 00016322     EISSN: 14320533     Source Type: Journal    
DOI: 10.1007/s00401-015-1412-5     Document Type: Article

References (31)

1. Arai T, Hasegawa M, Akiyama H, Ikeda K, Nonaka T, Mori H, Mann D, Tsuchiya K, Yoshida M, Hashizume Y et al (2006) 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. doi:10.1016/j.bbrc.2006.10.093
2. Ayala YM, De Conti L, Avendano-Vazquez SE, Dhir A, Romano M, D’Ambrogio A, Tollervey J, Ule J, Baralle M, Buratti E et al (2011) TDP-43 regulates its mRNA levels through a negative feedback loop. EMBO J 30:277–288. doi:10.1038/emboj.2010.310
3. Baralle M, Buratti E, Baralle FE (2013) The role of TDP-43 in the pathogenesis of ALS and FTLD. Biochem Soc Trans 41:1536–1540
4. Bose JK, Wang I-F, Hung L, Tarn W-Y, Shen C-KJ (2008) TDP-43 overexpression enhances exon 7 inclusion during the survival of motor neuron pre-mRNA splicing. J Biol Chem 283:28852–28859
5. Brettschneider J, Del Tredici K, Irwin DJ, Grossman M, Robinson JL, Toledo JB, Fang L, Van Deerlin VM, Ludolph AC, Lee VM et al (2014) Sequential distribution of pTDP-43 pathology in behavioral variant frontotemporal dementia (bvFTD). Acta Neuropathol. doi:10.1007/s00401-013-1238-y
6. Buratti E, Baralle FE (2001) Characterization and functional implications of the RNA binding properties of nuclear factor TDP-43, a novel splicing regulator of CFTR exon 9. J Biol Chem 276:36337–36343
7. Buratti E, Dörk T, Zuccato E, Pagani F, Romano M, Baralle FE (2001) Nuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping. EMBO J 20:1774–1784
8. Chang Y-F, Imam JS, Wilkinson MF (2007) The nonsense-mediated decay RNA surveillance pathway. Annu Rev Biochem 76:51–74
9. Che MX, Jiang YJ, Xie YY, Jiang LL, Hu HY (2011) Aggregation of the 35-kDa fragment of TDP-43 causes formation of cytoplasmic inclusions and alteration of RNA processing. FASEB J Off Publ Fed Am Soc Exp Biol 25:2344–2353. doi:10.1096/fj.10-174482
10. DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, Nicholson AM, Finch NA, Flynn H, Adamson J et al (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72:245–256. doi:10.1016/j.neuron.2011.09.011
11. Dormann D, Capell A, Carlson AM, Shankaran SS, Rodde R, Neumann M, Kremmer E, Matsuwaki T, Yamanouchi K, Nishihara M et al (2009) 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. doi:10.1111/j.1471-4159.2009.06211.x
12. Higashi S, Iseki E, Yamamoto R, Minegishi M, Hino H, Fujisawa K, Togo T, Katsuse O, Uchikado H, Furukawa Y (2007) Appearance pattern of TDP-43 in Japanese frontotemporal lobar degeneration with ubiquitin-positive inclusions. Neurosci Lett 419:213–218
13. Hiji M, Takahashi T, Fukuba H, Yamashita H, Kohriyama T, Matsumoto M (2008) White matter lesions in the brain with frontotemporal lobar degeneration with motor neuron disease: TDP-43-immunopositive inclusions co-localize with p62, but not ubiquitin. Acta Neuropathol 116:183–191
14. Mercado PA, Ayala YM, Romano M, Buratti E, Baralle FE (2005) Depletion of TDP 43 overrides the need for exonic and intronic splicing enhancers in the human apoA-II gene. Nucleic Acids Res 33:6000–6010. doi:10.1093/nar/gki897
15. Neumann M, Mackenzie IR, Cairns NJ, Boyer PJ, Markesbery WR, Smith CD, Taylor JP, Kretzschmar HA, Kimonis VE, Forman MS (2007) TDP-43 in the ubiquitin pathology of frontotemporal dementia with VCP gene mutations. J Neuropathol Exp Neurol 66:152–157
16. Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM et al (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314:130–133. doi:10.1126/science.1134108
17. Nishimoto Y, Ito D, Yagi T, Nihei Y, Tsunoda Y, Suzuki N (2010) Characterization of alternative isoforms and inclusion body of the TAR DNA-binding protein-43. J Biol Chem 285:608–619. doi:10.1074/jbc.M109.022012
18. Polymenidou M, Lagier-Tourenne C, Hutt KR, Huelga SC, Moran J, Liang TY, Ling SC, Sun E, Wancewicz E, Mazur C et al (2011) Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43. Nat Neurosci 14:459–468. doi:10.1038/nn.2779
19. Rademakers R, Neumann M, Mackenzie IR (2012) Advances in understanding the molecular basis of frontotemporal dementia. Nat Rev Neurol 8:423–434
20. Renton AE, Majounie E, Waite A, Simon-Sanchez J, Rollinson S, Gibbs JR, Schymick JC, Laaksovirta H, van Swieten JC, Myllykangas L et al (2011) A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72:257–268. doi:10.1016/j.neuron.2011.09.010
21. Robertson J, Doroudchi MM, Nguyen MD, Durham HD, Strong MJ, Shaw G, Julien J-P, Mushynski WE (2003) A neurotoxic peripherin splice variant in a mouse model of ALS. J Cell Biol 160:939–949
22. Sanelli T, Xiao S, Horne P, Bilbao J, Zinman L, Robertson J (2007) Evidence that TDP-43 is not the major ubiquitinated target within the pathological inclusions of amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 66:1147–1153. doi:10.1097/nen.0b013e31815c5edd
23. Shiina Y, Arima K, Tabunoki H, Satoh J (2010) TDP-43 dimerizes in human cells in culture. Cell Mol Neurobiol 30:641–652. doi:10.1007/s10571-009-9489-9
24. Udan M, Baloh RH (2011) Implications of the prion-related Q/N domains in TDP-43 and FUS. Prion 5:1–5
25. Wang HY, Wang IF, Bose J, Shen CK (2004) Structural diversity and functional implications of the eukaryotic TDP gene family. Genomics 83:130–139
26. Winton MJ, Igaz LM, Wong MM, Kwong LK, Trojanowski JQ, Lee VM (2008) Disturbance of nuclear and cytoplasmic TAR DNA-binding protein (TDP-43) induces disease-like redistribution, sequestration, and aggregate formation. J Biol Chem 283:13302–13309. doi:10.1074/jbc.M800342200
27. Xi Z, Zinman L, Grinberg Y, Moreno D, Sato C, Bilbao JM, Ghani M, Hernández I, Ruiz A, Boada M (2012) Investigation of c9orf72 in 4 neurodegenerative disorders. Arch Neurol 69:1583–1590
28. Xiao S, Tjostheim S, Sanelli T, McLean JR, Horne P, Fan Y, Ravits J, Strong MJ, Robertson J (2008) An aggregate-inducing peripherin isoform generated through intron retention is upregulated in amyotrophic lateral sclerosis and associated with disease pathology. J Neurosci 28:1833–1840
29. Yang C, Tan W, Whittle C, Qiu L, Cao L, Akbarian S, Xu Z (2010) The C-terminal TDP-43 fragments have a high aggregation propensity and harm neurons by a dominant-negative mechanism. PLoS One 5:e15878. doi:10.1371/journal.pone.0015878
30. Yokota O, Davidson Y, Bigio EH, Ishizu H, Terada S, Arai T, Hasegawa M, Akiyama H, Sikkink S, Pickering-Brown S (2010) Phosphorylated TDP-43 pathology and hippocampal sclerosis in progressive supranuclear palsy. Acta Neuropathol 120:55–66
31. Zhang YJ, Xu YF, Dickey CA, Buratti E, Baralle F, Bailey R, Pickering-Brown S, Dickson D, Petrucelli L (2007) Progranulin mediates caspase-dependent cleavage of TAR DNA binding protein-43. J Neurosci Off J Soc Neurosci 27:10530–10534. doi:10.1523/JNEUROSCI.3421-07.2007