Disruption of alpha-mannosidase processing induces non-canonical hybrid-type glycosylation

Crispin M, Aricescu AR, Chang VT, Jones EY, Stuart DI, Dwek RA, Davis SJ, Harvey DJ. (2007), FEBS Lett. 581, 1963-8

Abstract

Golgi alpha-mannosidase II is essential for the efficient formation of complex-type glycosylation. Here, we demonstrate that the disruption of Golgi alpha-mannosidase II activity by swainsonine in human embryonic kidney cells is capable of inducing a novel class of hybrid-type glycosylation containing a partially processed mannose moiety. The discovery of ‘Man(6)-based’ hybrid-type glycans reveals a broader in vivo specificity of N-acetylglucosaminyltransferase I, further defines the arm-specific tolerance of core alpha1-6 fucosyltransferase to terminal alpha1-2 mannose residues, and suggests that disruption of Golgi alpha-mannosidase II activity is capable of inducing potentially ‘non-self’ structures.

Key figure: Structures of the glycans whose fragmentation is discussed in this paper

Key to symbols used to represent monosaccharide constituents in this and subsequent figures: (◊) Gal, (■) GlcNAc, (○) Man, () Fuc. The linkage position is shown by the angle of the lines linking the sugar residues (vertical line = 2-link, forward slash = 3-link, horizontal line = 4-link, back slash = 6-link). Anomericity is indicated by full lines for β-bonds and broken lines for α-bonds. Terminal α1-2 mannose residues of Man₉GlcNAc₂ are termed the D1, D2 and D3 residues (illustrated on the monoglucosylated Man₉GlcNAc₂, compound 7) [31], [32] and [33]. This labelling is distinct from the ion nomenclature of Domon and Costello [28].