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Developmental and Hormonal Regulation of Protein N-Glycosylation in the Mammary Gland

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Abstract

Glycosylation represents the most commonconjugation of both membrane-bound and secreted proteinsof animal cells. Among the different types ofglycosylation, the N-linked attachment of sugars to thepolypeptide backbone is by far the most abundantmodification. The biosynthesis of the precursorcarbohydrate unit of these proteins is initiated by astepwise assembly ofGlc3Man9Glc2NAc P-P-Dolin the dolichol cycle, its transfer en bloc to the nascent polypeptidein the rough endoplasmic reticulum (RER),3followed by excision of the glucosyl residues byprocessing-specific enzymes, glucosidase I and II, alsoresident in the endoplasmic reticulum. Additionalposttranslational modifications of the carbohydratemoiety in the RER, Golgi, and trans -Golgi network,differ for individual glycoproteins for the completionof final products as high mannose, complex orhybrid glycoproteins en route to their finaldestinations in the secretory pathway. The enzymeGlcNAc-1-P transferase (GPT) catalyzes the first andcommitted step, i.e., the transfer of GlcNAc-1-P fromUDP-GlcNAc to Dol-P to form GlcNAc-P-PDol, in theassembly of the oligosaccharide precursor. GlucosidaseI triggers the maturation phase by clipping the distalα 1,2-linked Glc residue on the incipientglycoprotein. The critical juxtaposition of the twoenzymes in the multistep pathway makes them excellentcandidates for the overall regulation of proteinN-glycosylation. The highly elevated needs of glycosylationduring lactation demand regulation of glycosylation inthe gland over and above the levels in the quiescent,virgin and postlactating, regressed gland.

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  1. Inder K. Vijay
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Vijay, I.K. Developmental and Hormonal Regulation of Protein N-Glycosylation in the Mammary Gland. J Mammary Gland Biol Neoplasia 3, 325–336 (1998). https://doi.org/10.1023/A:1018771628925

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