Ataxin-10 interacts with O-linked beta-N-acetylglucosamine transferase in the brain.
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.
März
Pia
P
Institute of Physiology, Pestalozzistr. 20, University of Basel, CH-4056 Basel, Switzerland.
Stetefeld
Jörg
J
Bendfeldt
Kerstin
K
Nitsch
Cordula
C
Reinstein
Jochen
J
Shoeman
Robert L
RL
Dimitriades-Schmutz
Beatrice
B
Schwager
Martine
M
Leiser
Dominic
D
Ozcan
Sabire
S
Otten
Uwe
U
Ozbek
Suat
S
D000117:Acetylglucosamine / Q000378:metabolism; D000118:Acetylglucosaminidase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000067736:Ataxin-10; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D002850:Chromatography, Gel; D003600:Cytosol / Q000378:metabolism; D006031:Glycosylation; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D010673:Pheochromocytoma; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D001619:beta-N-Acetylhexosaminidases
D000067736:Ataxin-10; C496258:Atxn10 protein, rat; D009097:Multienzyme Complexes; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D051548:Histone Acetyltransferases; C110628:hexosaminidase C; D000118:Acetylglucosaminidase; D001619:beta-N-Acetylhexosaminidases; D000117:Acetylglucosamine