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