Expanded polyglutamines impair synaptic transmission and ubiquitin–proteasome system in Caenorhabditis elegans
Article first published online: 22 MAY 2006
Journal of Neurochemistry
Volume 98, Issue 2, pages 576–587, July 2006
How to Cite
Khan, L. A., Bauer, P. O., Miyazaki, H., Lindenberg, K. S., Landwehrmeyer, B. G. and Nukina, N. (2006), Expanded polyglutamines impair synaptic transmission and ubiquitin–proteasome system in Caenorhabditis elegans. Journal of Neurochemistry, 98: 576–587. doi: 10.1111/j.1471-4159.2006.03895.x
- Issue published online: 22 MAY 2006
- Article first published online: 22 MAY 2006
- Received December 16, 2005; revised manuscript received February 17, 2006; accepted March 14, 2006.
- Caenorhabditis elegans;
- neurodegenerative disease;
Polyglutamine (polyQ) expansion in many proteins, including huntingtin and ataxin-3, is pathogenic and responsible for neuronal dysfunction and degeneration. Although at least nine neurodegenerative diseases are caused by expanded polyQ, the pathogenesis of these diseases is still not well understood. In the present study, we used Caenorhabditis elegans to study the molecular mechanism of polyQ-mediated toxicity. We expressed full-length and truncated ataxin-3 with different lengths of polyQ in the nervous system of C. elegans. We show that expanded polyQ interrupts synaptic transmission, and induces swelling and aberrant branching of neuronal processes. Using an ubiquitinated fluorescence reporter construct, we also showed that polyQ aggregates impair the ubiquitin–proteasome system in C. elegans. These results may provide information for further understanding the pathogenesis of polyQ diseases.