Role of spacer-1 in the maturation and function of GlcNAc-1-phosphotransferase

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3 Scopus citations

Abstract

The UDP-GlcNAc:lysosomal enzyme, N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-PT), is an α2β2γ2 hexamer that mediates the initial step in the formation of the mannose 6-phosphate targeting signal on newly synthesized lysosomal acid hydrolases. The GNPTAB gene encodes the 1256 amino acid long α/β precursor which is normally cleaved at K928 in the early Golgi by Site-1 protease (S1P). Here, we show that removal of the so-called ‘spacer-1′ domain (residues 86–322) results in cleavage almost exclusively at a second S1P consensus sequence located upstream of K928. In addition, GlcNAc-1-PT lacking spacer-1 exhibits enhanced phosphorylation of several non-lysosomal glycoproteins, while the phosphorylation of lysosomal acid hydrolases is not altered. In view of these effects on the maturation and function of GlcNAc-1-PT, we suggest renaming `spacer-1′ the `regulatory-1′ domain.

Original languageEnglish
Pages (from-to)47-55
Number of pages9
JournalFEBS Letters
Volume591
Issue number1
DOIs
StatePublished - Jan 1 2017

Keywords

  • GlcNAc-1-phosphotransferase
  • lysosomal enzyme
  • mannose 6-phosphate
  • site-1 protease
  • spacer domain

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