Cellular defects and altered gene expression in PC12 cells stably expressing mutant huntingtin
| Autor: | Anna L. Cheng, He Li, Shihua Li, Xiao-Jiang Li |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Cellular pathology
Huntingtin Neurite Cell Survival Mutant Apoptosis Nerve Tissue Proteins Biology Transfection PC12 Cells Article Gene expression Neurites Animals Nerve Growth Factors RNA Messenger Microscopy Immunoelectron Cell Size Cell Nucleus Neurons Differential display Huntingtin Protein General Neuroscience Nuclear Proteins Exons Staurosporine Molecular biology Peptide Fragments Cell biology Rats Gene Expression Regulation Cytoplasm Mutation Peptides Protein Binding |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 19(13) |
| ISSN: | 0270-6474 |
| Popis: | Expanded polyglutamine tracts cause huntingtin and other proteins to accumulate and aggregate in neuronal nuclei. Whether the intranuclear aggregation or localization of a polyglutamine protein initiates cellular pathology remains controversial. We established stably transfected pheochromocytoma PC12 cells that express the N-terminal fragment of huntingtin containing 20 (20Q) or 150 (150Q) glutamine residues. The 150Q protein is predominantly present in the nuclei, whereas the 20Q protein is distributed throughout the cytoplasm. Electron microscopic examination confirmed that most of the 150Q protein is diffuse in the nucleus with very few microscopic aggregates observed. Compared with parental PC12 cells and cells expressing 20Q, cells expressing 150Q display abnormal morphology, lack normal neurite development, die more rapidly, and are more susceptible to apoptotic stimulation. The extent of these cellular defects in 150Q cells is correlated with the expression level of the 150Q protein. Differential display PCR and expression studies show that cells expressing 150Q have altered expression of multiple genes, including those that are important for neurite outgrowth. Our study suggests that mutant huntingtin in the nucleus is able to induce multiple cellular defects by interfering with gene expression even in the absence of aggregation. |
| Databáze: | OpenAIRE |
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