Role of spacer‐1 in the maturation and function of GlcNAc‐1‐phosphotransferase. Issue 1 (1st January 2017)

• Record Type: Journal Article
• Authors: Liu, Lin; Lee, Wang‐Sik; Doray, Balraj; Kornfeld, Stuart
• Is Part Of: FEBS letters. Volume 591:Issue 1(2017)
• Page Start: 47
• Page End: 55
• Publication Date: 2017-01-01
• Subjects: GlcNAc‐1‐phosphotransferase -- lysosomal enzyme -- mannose 6‐phosphate -- site‐1 protease -- spacer domain; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.12525
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : The UDP‐GlcNAc:lysosomal enzyme, N ‐acetylglucosamine‐1‐phosphotransferase (GlcNAc‐1‐PT), is an α2 β2 γ2 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. Abstract :