Abstract
Glycoproteins play critical roles in brain development, including particularly neuronal and glial differentiation. However, little is known about the regulation of glycoprotein synthesis in developing brain. Glycoprotein biosynthesis is known to occur via the dolichol-linked pathway, in which dolichyl phosphate (dol-P) is the critical intermediate. In this work we utilized developing rat brain to study the regulation of dolichollinked glycoprotein biosynthesis. Utilization of a new technique based upon high performance liquid chromatography led to the definition of a striking increase in brain content of dol-P in the 2nd to 4th weeks of postnatal development. Values increased 10-fold from 10 days of life-to 25 days of life. Strikingly, specific activity of dolichol kinase, the enzyme that catalyzes formation of dol-P from dolichol and cytidine triphosphate, exhibited a parallel developmental increase. Similarly, the specific activity of the first committed enzyme in the transfer of saccharide moieties to dol-P, the tunicamycin-sensitive N-acetylglucosaminylphosphotransferase, also exhibited a sharp developmental increase in the 2nd to <4th weeks. Taken together the data indicate for the first time that dolichol kinase is the critical determinant of dol-P levels in brain, and that coordinate activation of the dolichol-1inked pathway to glycoproteins occurs at a developmental time period which includes neuronal and glial differentiation. (Supported by NIH-ROI-HD07464).
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Volpe, J., Sakakihara, Y. & Rust, R. COORDINATE ACTIVATION OF THE DOLICHOL-LINKED PATHWAY TO GLYCOPROTEINS IN DEVELOPING BRAIN. Pediatr Res 21 (Suppl 4), 223 (1987). https://doi.org/10.1203/00006450-198704010-00342
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DOI: https://doi.org/10.1203/00006450-198704010-00342