Expanded polyglutamines impair synaptic transmission and ubiquitin-proteasome system in Caenorhabditis elegans

Liakot A. Khan, Peter O. Bauer, Haruko Miyazaki, Katrin S. Lindenberg, Bernhard G. Landwehrmeyer, Nobuyuki Nukina

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)576-587
Number of pages12
JournalJournal of Neurochemistry
Volume98
Issue number2
DOIs
Publication statusPublished - Jul 2006
Externally publishedYes

Keywords

  • Caenorhabditis elegans
  • Neurodegenerative disease
  • Polyglutamine

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint

Dive into the research topics of 'Expanded polyglutamines impair synaptic transmission and ubiquitin-proteasome system in Caenorhabditis elegans'. Together they form a unique fingerprint.

Cite this