A congenital disorder of deglycosylation: Biochemical characterization of N-glycanase 1 deficiency in patient fibroblasts.

Abstract:

:N-Glycanase 1, encoded by NGLY1, catalyzes the deglycosylation of misfolded N-linked glycoproteins retrotranslocated into the cytosol. We identified nine cases with mutations in NGLY1. The patients show developmental delay, seizures, peripheral neuropathy, abnormal liver function and alacrima (absence of tears). The mutations in NGLY1 resulted in the absence of N-glycanase 1 protein in patient-derived fibroblasts. Applying a recently established cellular deglycosylation-dependent Venus fluorescence assay, we found that patient fibroblasts had dramatically reduced fluorescence, indicating a pronounced reduction in N-glycanase enzymatic activity. Using this assay, we could find no evidence of other related activities. Our findings reveal that NGLY1 mutations destroy both N-glycanase 1 protein and enzymatic activity.

journal_name

Glycobiology

journal_title

Glycobiology

authors

He P,Grotzke JE,Ng BG,Gunel M,Jafar-Nejad H,Cresswell P,Enns GM,Freeze HH

doi

10.1093/glycob/cwv024

subject

Has Abstract

pub_date

2015-08-01 00:00:00

pages

836-44

issue

8

eissn

0959-6658

issn

1460-2423

pii

cwv024

journal_volume

25

pub_type

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