Nervous System & Sugar Chain

Lectins Involved in the Quality Control System of Glycoproteins

 Carbohydrate chains attached to proteins play key roles in intracellular and extracellular processes. Several types of sugar moieties including N- and O-glycans have vital biological functions outside the cells. In contrast, high mannose-type N-glycans, especially those of higher molecular mass, are essential for the quality control, trafficking and sorting of glycoproteins in the cells. Formation of a lipid-linked precursor oligosaccharide and en bloc transfer to a nascent polypeptide in the endoplasmic reticulum (ER) is conserved in both lower and higher organisms. Such a glycosylation step is unique to N-glycans compared to other types of sugar chains modified by stepwise addition. The processing of N- and O-linked oligosaccharides in the Golgi apparatus occurs in highly divergent steps mediated by hundreds of glycosyltransferases and glycan structures thus produced differs by species, organs and several conditions. By clarifying the diversity and unity of such glycosylation steps, we can easily understand the functions of glycans attached to proteins.

Among a large amount of newly synthesized proteins in the ER, 30% of them have not reached a correctly folded conformation and accumulation of these proteins potentially causes damage to the cells. To prevent the exit of folding intermediates and incompletely assembled proteins from the ER, (1) incomplete folding or misfolding proteins are bound again by molecular chaperones and folding enzymes, (2) misfolded proteins persistently are retro-translocated form the ER into the cytosol and are degraded by proteasomes, (3) proteins folded and matured properly exit from the ER, (4) individual protein species or protein families are sorted to their final destinations. Conformation-specific retention, export and sorting of a large number of newly synthesized proteins, which is called "quality control," are regulated by very few types of intracellular lectins.

In this series, several lectins or lectin-like molecules involved in the quality control system of glycoproteins are described based on the molecular nature, especially domain structures, regulation of activity, associated molecules in their function, and dynamic localization in the cells.
Kazuo Yamamoto (Graduate School of Frontier Sciences, University of Tokyo)
References (1) Helenius A, Aebi M: Intracellular functions of N-linked glycans. Science, 291, 2364-2369, 2001
(2) Hauri H, Appenzeller C, Kuhn F, Nufer O: Lectins and traffic in the secretory pathway. FEBS lett., 476, 32-37, 2000
(3) Yamamoto, K. Intracellular transport and sorting of glycoproteins by cargo receptors. Seikagaku (in Japanese), 76, 240-255, 2004
Oct. 30, 2005

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