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

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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Liu L,Lee WS,Doray B,Kornfeld S

doi

10.1002/1873-3468.12525

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

47-55

issue

1

eissn

0014-5793

issn

1873-3468

journal_volume

591

pub_type

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