Expanded polyglutamines impair synaptic transmission and ubiquitin-proteasome system in Caenorhabditis elegans.
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.
Khan
Liakot A
LA
Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, Saitama, Japan.
Bauer
Peter O
PO
Miyazaki
Haruko
H
Lindenberg
Katrin S
KS
Landwehrmeyer
Bernhard G
BG
Nukina
Nobuyuki
N
D000818:Animals; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000502:physiology*; D016923:Cell Death; D002460:Cell Line; D005456:Fluorescent Dyes; D006801:Humans; D007150:Immunohistochemistry; D007814:Larva / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*; D014162:Transfection; D025801:Ubiquitin / Q000502:physiology*
D005456:Fluorescent Dyes; D010455:Peptides; D025801:Ubiquitin; C097188:polyglutamine; D046988:Proteasome Endopeptidase Complex