Stable-tau overexpression in human neuroblastoma cells: an open door for explaining neuronal death in tauopathies.
Many neurodegenerative disorders referred to as "tauopathies" are characterized by the accumulation and aggregation of Tau proteins into filaments. In these pathologies, Tau proteins are hyperphosphorylated and also abnormally phosphorylated. Moreover, they differ from each other by the preferential aggregation of isoforms exhibiting either three microtubule-binding repeats (3R) or four repeats (4R) Tau. To investigate the effects of an intracellular accumulation of Tau, we stably transfected neuroblastoma cell line SY5Y with either 3R or 4R Tau. Our data showed that an increase in intracellular Tau expression has led to their hyperphosphorylation. Conversely, an abnormal Tau phosphorylation and/or aggregation were never observed. Furthermore, SY5Y cells transfected with 4R Tau showed an increased susceptibility to cell death. Finally, in apoptotic conditions, Tau proteins were degraded at their carboxy terminus by caspase, leading to an apparent decrease in Tau phosphorylation in this region. Because truncated Tau generated during apoptosis are not commonly found in Tau aggregates, apoptotic processes may not be of interest in neurofibrillary degeneration.
Delobel
Patrice
P
INSERM U422, Institut de Medecine Prédictive et Recherche Thérapeutique, Place de Verdun, F-59045 Lille cedex, France.
Mailliot
Christel
C
Hamdane
Malika
M
Sambo
Anne-Véronique
AV
Bégard
Séverine
S
Violleau
Anne
A
Delacourte
André
A
Buée
Luc
L
D017209:Apoptosis / Q000502:physiology*; D016923:Cell Death / Q000502:physiology*; D045744:Cell Line, Tumor; D006801:Humans; D009447:Neuroblastoma; D019636:Neurodegenerative Diseases / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D024801:Tauopathies / Q000235:genetics / Q000473:pathology; D014162:Transfection; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D011994:Recombinant Proteins; D016875:tau Proteins