Ataxin-10 interacts with O-linked β-N-acetylglucosamine transferase in the brain

Pia März, Jörg Stetefeld, Kerstin Bendfeldt, Cordula Nitsch, Jochen Reinstein, Robert L. Shoeman, Beatrice Dimitriades-Schmutz, Martine Schwager, Dominic Leiser, Sabire Özcan, Uwe Otten, Suat Özbek

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Modification by O-GlcNAc involves a growing number of eucaryotic nuclear and cytosolic proteins. Glycosylation of intracellular proteins is a dynamic process that in several cases competes with and acts as a reciprocal modification system to phosphorylation. O-Linked β-N-acetylglucosamine transferase (OGT) levels are highest in the brain, and neurodegenerative disorders such as Alzheimer disease have been shown to involve abnormally phosphorylated key proteins, probably as a result of hypoglycosylation. Here, we show that the neurodegenerative disease protein ataxin-10 (Atx-10) is associated with cytoplasmic OGT p110 in the brain. In PC12 cells and pancreas, this association is competed by the shorter OGT p78 splice form, which is down-regulated in brain. Overexpression of Atx-10 in PC12 cells resulted in the reconstitution of the Atx-10-OGT p110 complex and enhanced intracellular glycosylation activity. Moreover, in an in vitro enzyme assay using PC12 cell extracts, Atx-10 increased OGT activity 2-fold. These data indicate that Atx-10 might be essential for the maintenance of a critical intracellular glycosylation level and homeostasis in the brain.

Original languageEnglish
Pages (from-to)20263-20270
Number of pages8
JournalJournal of Biological Chemistry
Volume281
Issue number29
DOIs
StatePublished - Jul 21 2006

Bibliographical note

Funding Information:
This work was supported by Grant AV0Z5039906 from the Academy of Sciences of the Czech Republic and Grant 111100003 from The Ministry of Education, Youth and Sports MSM.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Ataxin-10 interacts with O-linked β-N-acetylglucosamine transferase in the brain'. Together they form a unique fingerprint.

Cite this