Although the role of the microtubule-binding domain of the tau protein in the modulation of microtubule assembly is widely established, other possible functions of this protein have been poorly investigated. We have analyzed the effect of adenovirally mediated expression of two fragments of the N-terminal portion - free of microtubule-binding domain - of the tau protein in cerebellar granule neurons (CGNs). We found that while the expression of the tau (1-230) fragment, as well as of full-length tau, inhibits the onset of apoptosis, the tau (1-44) fragment exerts a powerful toxic action on the same neurons. The antiapoptotic action of tau (1-230) is exerted at the level of Akt-mediated activation of the caspase cascade. On the other hand, the toxic action of the (1-44) fragment is not prevented by inhibitors of CGN apoptosis, but is fully inhibited by NMDA receptor antagonists. These findings point to a novel, physiological role of the N-terminal domain of tau, but also underlay that its possible proteolytic truncation mediated by apoptotic proteases may generate a highly toxic fragment that could contribute to neuronal death.

Amadoro, G., Serafino, A., Barbato, C., Ciotti, M., Sacco, A., Calissano, P., et al. (2004). Role of N-terminal tau domain integrity on the survival of cerebellar granule neurons. CELL DEATH AND DIFFERENTIATION, 11(2), 217-230 [10.1038/sj.cdd.4401314].

Role of N-terminal tau domain integrity on the survival of cerebellar granule neurons

CALISSANO, PIETRO;CANU, NADIA
2004-02-11

Abstract

Although the role of the microtubule-binding domain of the tau protein in the modulation of microtubule assembly is widely established, other possible functions of this protein have been poorly investigated. We have analyzed the effect of adenovirally mediated expression of two fragments of the N-terminal portion - free of microtubule-binding domain - of the tau protein in cerebellar granule neurons (CGNs). We found that while the expression of the tau (1-230) fragment, as well as of full-length tau, inhibits the onset of apoptosis, the tau (1-44) fragment exerts a powerful toxic action on the same neurons. The antiapoptotic action of tau (1-230) is exerted at the level of Akt-mediated activation of the caspase cascade. On the other hand, the toxic action of the (1-44) fragment is not prevented by inhibitors of CGN apoptosis, but is fully inhibited by NMDA receptor antagonists. These findings point to a novel, physiological role of the N-terminal domain of tau, but also underlay that its possible proteolytic truncation mediated by apoptotic proteases may generate a highly toxic fragment that could contribute to neuronal death.
11-feb-2004
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/09 - FISIOLOGIA
English
Alzheimer's disease; apoptosis inhibitor; caspase; microtubule protein; n methyl dextro aspartic acid receptor blocking agent; protein kinase B; tau protein; Adenovirus; amino terminal sequence; animal cell; apoptosis; article; cell survival; cerebellum; controlled study; enzyme activation; granule cell; nerve cell necrosis; nonhuman; priority journal; protein degradation; protein domain; protein expression; rat; Animals; Apoptosis; Caspases; Cell Survival; Cells, Cultured; Enzyme Activation; Free Radical Scavengers; Gene Expression; Humans; Neurons; Peptide Fragments; Phosphoserine; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar; Reactive Oxygen Species; Receptors, N-Methyl-D-Aspartate; tau Proteins; Adenoviridae; Animalia
Amadoro, G., Serafino, A., Barbato, C., Ciotti, M., Sacco, A., Calissano, P., et al. (2004). Role of N-terminal tau domain integrity on the survival of cerebellar granule neurons. CELL DEATH AND DIFFERENTIATION, 11(2), 217-230 [10.1038/sj.cdd.4401314].
Amadoro, G; Serafino, A; Barbato, C; Ciotti, M; Sacco, A; Calissano, P; Canu, N
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
4401314.pdf

accesso aperto

Licenza: Copyright dell'editore
Dimensione 708.49 kB
Formato Adobe PDF
708.49 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/57410
Citazioni
  • ???jsp.display-item.citation.pmc??? 26
  • Scopus 67
  • ???jsp.display-item.citation.isi??? 60
social impact