Functions of the α, β, and γsubunits of UDP-GlcNAc:Lysosomal enzyme N-acetylglucosamine-1-phosphotransferase

Yi Qian, Intaek Lee, Wang Sik Lee, Meiqian Qian, Mariko Kudo, William M. Canfield, Peter Lobel, Stuart Kornfeld

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase is an α2β2γ2 hexamer that mediates the first step in the synthesis of the mannose 6-phosphate recognition marker on lysosomal acid hydrolases. Using a multifaceted approach, including analysis of acid hydrolase phosphorylation in mice and fibroblasts lacking the γ subunit along with kinetic studies of recombinant α2β 2γ2 and α2β2 forms of the transferase, we have explored the function of the α/βand γ subunits. The findings demonstrate that the α/β subunits recognize the protein determinant of acid hydrolases in addition to mediating the catalytic function of the transferase. In mouse brain, the α/βsubunits phosphorylate about one-third of the acid hydrolases at close to wild-type levels but require the γ subunit for optimal phosphorylation of the rest of the acid hydrolases. In addition to enhancing the activity of the α/β subunits toward a subset of the acid hydrolases, the γ subunit facilitates the addition of the second GlcNAc-P to high mannose oligosaccharides of these substrates. We postulate that the mannose 6-phosphate receptor homology domain of the γ subunit binds and presents the high mannose glycans of the acceptor to the α/β catalytic site in a favorable manner.

Original languageEnglish
Pages (from-to)3360-3370
Number of pages11
JournalJournal of Biological Chemistry
Volume285
Issue number5
DOIs
StatePublished - Jan 29 2010

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