Time course of polyglutamine aggregate body formation and cell death: Enhanced growth in nucleus and an interval for cell death

Polyglutamine (polyQ) aggregate bodies are a hallmark of dentatorubral‐pallidoluysian atrophy and related neurodegenerative disorders, although the relationship between aggregate body formation and cell death is not clear. We analyzed the kinetics of polyQ aggregate formation and the time intervals...

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Published in:Journal of neuroscience research 2002-05, Vol.68 (4), p.442-448
Main Authors: Toyoshima, I., Sugawara, M., Kato, K., Wada, C., Shimohata, T., Koide, R., Onodera, O., Tsuji, S.
Format: Article
Language:English
Subjects:
Animals
Cell Death
Cell Nucleus - metabolism
Cell Nucleus - pathology
COS Cells
Cytoplasm - metabolism
Cytoplasm - pathology
DRPLA
fluorescence video microscopy
green fluorescent protein
Green Fluorescent Proteins
Indicators and Reagents
Luminescent Proteins
Microscopy, Video
Nerve Tissue Proteins - metabolism
neuronal intranuclear inclusion
Peptides - metabolism
polyglutamine stretch
Time Factors
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Summary:Polyglutamine (polyQ) aggregate bodies are a hallmark of dentatorubral‐pallidoluysian atrophy and related neurodegenerative disorders, although the relationship between aggregate body formation and cell death is not clear. We analyzed the kinetics of polyQ aggregate formation and the time intervals for cell death, tracking individual cells using fluorescence video microscopy, for the first time. Expanded polyQ tracts of atrophin‐1 with or without nuclear localization signal (NLS) labeled with green fluorescent protein (GFP) were constructed, Q57NLS/GFP and Q56/GFP, respectively. All of the Q57NLS/GFP aggregate bodies were in nuclei, and all of the Q56/GFP aggregate bodies were in cytoplasm. Aggregates of Q56/GFP were larger than those of Q57NLS/GFP. Surprisingly, a kinetic analysis showed that the latter grew 5.37 times faster than the former. The time interval between transfection and cell death was shorter in Q57NLS/GFP, but the time between the end of the rapid growing phase of aggregation and the start of the cell death process did not show a significant difference. Aggregate growth was confirmed to correspond to the accumulated free polyQ by the time of starting aggregation. These findings suggest that aggregate body formation induced by expanded polyQ stretches is a self‐limiting process and is enhanced by factor(s) in nuclei, whereas it is not tightly bound to the cell death process. © 2002 Wiley‐Liss, Inc.
ISSN:0360-4012
1097-4547
DOI:10.1002/jnr.10233