Multiple domains of GlcNAc-1-phosphotransferase mediate recognition of lysosomal enzymes

Eline Van Meel, Wang Sik Lee, Lin Liu, Yi Qian, Balraj Doray, Stuart Kornfeld

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The Golgi enzyme UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine- 1-phosphotransferase (GlcNAc-1-phosphotransferase), an α2β2γ2 hexamer, mediates the initial step in the addition of the mannose 6-phosphate targeting signal on newly synthesized lysosomal enzymes. This tag serves to direct the lysosomal enzymes to lysosomes. A key property of GlcNAc-1-phosphotransferase is its unique ability to distinguish the 60 or so lysosomal enzymes from the numerous nonlysosomal glycoproteins with identical Asn-linked glycans. In this study, we demonstrate that the two Notch repeat modules and the DNA methyltransferase-associated protein interaction domain of the α subunit are key components of this recognition process. Importantly, different combinations of these domains are involved in binding to individual lysosomal enzymes. This study also identifies the γ-binding site on the α subunit and demonstrates that in the majority of instances the mannose 6-phosphate receptor homology domain of the γ subunit is required for optimal phosphorylation. These findings serve to explain how GlcNAc-1-phosphotransferase recognizes a large number of proteins that lack a common structural motif.

Original languageEnglish
Pages (from-to)8295-8307
Number of pages13
JournalJournal of Biological Chemistry
Volume291
Issue number15
DOIs
StatePublished - Apr 8 2016

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