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

Pia März1, Jörg Stetefeld, Kerstin Bendfeldt

  • 1Institute of Physiology, Pestalozzistr. 20, University of Basel, CH-4056 Basel, Switzerland.

The Journal of Biological Chemistry
|May 23, 2006
PubMed

Insights

Ataxin-10 (Atx-10) interacts with O-linked beta-N-acetylglucosamine transferase (OGT) in the brain, enhancing intracellular glycosylation. This suggests Atx-10 is crucial for maintaining brain glycosylation homeostasis.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • O-GlcNAc modification impacts numerous eukaryotic nuclear and cytosolic proteins.
  • Intracellular protein glycosylation dynamically competes with and reciprocally modifies phosphorylation.
  • Elevated O-linked beta-N-acetylglucosamine transferase (OGT) levels are found in the brain, where altered phosphorylation is linked to neurodegenerative diseases like Alzheimer's, potentially due to reduced glycosylation.

Purpose of the Study:

  • To investigate the role of the neurodegenerative disease protein ataxin-10 (Atx-10) in intracellular glycosylation.
  • To determine the interaction between Atx-10 and OGT in neuronal cells.
  • To explore the functional consequences of Atx-10 and OGT interaction on glycosylation activity.

Main Methods:

  • Co-immunoprecipitation to detect Atx-10 and OGT complex formation in brain tissue and cell lines.
  • Analysis of OGT splice variants (p110 and p78) in different tissues.
  • Overexpression studies in PC12 cells to assess the impact on glycosylation activity.
  • In vitro enzyme assays to quantify OGT activity in the presence of Atx-10.

Main Results:

  • Ataxin-10 (Atx-10) was found to associate with the cytoplasmic OGT p110 splice form in the brain.
  • This Atx-10-OGT p110 interaction was competed by the shorter OGT p78 splice form, which is less abundant in the brain.
  • Overexpression of Atx-10 in PC12 cells reconstituted the Atx-10-OGT p110 complex and increased intracellular glycosylation.
  • In vitro assays demonstrated that Atx-10 enhances OGT activity twofold.

Conclusions:

  • Ataxin-10 (Atx-10) forms a complex with OGT p110 in the brain, suggesting a role in regulating intracellular glycosylation.
  • The interaction and activity of OGT may be modulated by Atx-10, impacting glycosylation levels.
  • Atx-10 is potentially essential for maintaining critical intracellular glycosylation levels and homeostasis within the brain.

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