Senataxin, the yeast Sen1p orthologue: characterization of a unique protein in which recessive mutations cause ataxia and dominant mutations cause motor neuron disease.

Published

Journal Article

A severe recessive cerebellar ataxia, Ataxia-Oculomotor Apraxia 2 (AOA2) and a juvenile onset form of dominant amyotrophic lateral sclerosis (ALS4) result from mutations of the Senataxin (SETX) gene. To begin characterization this disease protein, we developed a specific antibody to the DNA/RNA helicase domain of SETX. In murine brain, SETX concentrates in several regions, including cerebellum, hippocampus and olfactory bulb with a general neuronal expression profile, colocalizing with NeuN. In cultured cells, we found that SETX was cytoplasmically diffuse, but in the nucleus, SETX was punctate, colocalizing with fibrillarin, a marker of the nucleolus. In differentiated non-cycling cells, nuclear SETX was not restricted to the nucleolus but was diffuse within the nucleoplasm, suggesting cell-cycle-dependent localization. SETX missense mutations cluster within the N-terminus and helicase domains. Flag tagging at the N-terminus caused protein mislocation to the nucleoplasm and failure to export to the cytoplasm, suggesting that the N-terminus may be essential for correct SETX localization. We report here the first characterization of SETX protein, which may provide future insights into a new mechanism leading to neuron death.

Full Text

Duke Authors

Cited Authors

  • Chen, Y-Z; Hashemi, SH; Anderson, SK; Huang, Y; Moreira, M-C; Lynch, DR; Glass, IA; Chance, PF; Bennett, CL

Published Date

  • July 2006

Published In

Volume / Issue

  • 23 / 1

Start / End Page

  • 97 - 108

PubMed ID

  • 16644229

Pubmed Central ID

  • 16644229

International Standard Serial Number (ISSN)

  • 0969-9961

Digital Object Identifier (DOI)

  • 10.1016/j.nbd.2006.02.007

Language

  • eng

Conference Location

  • United States