Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Biochim Biophys Acta. 2009 Apr;1790(4):275-82. doi: 10.1016/j.bbagen.2009.01.006.

Protective protein/cathepsin A rescues N-glycosylation defects in neuraminidase-1.

Author information

  • 1Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.

Abstract

BACKGROUND:

Neuraminidase-1 (NEU1) catabolizes the hydrolysis of sialic acids from sialo-glycoconjugates. NEU1 depends on its interaction with the protective protein/cathepsin A (PPCA) for lysosomal compartmentalization and catalytic activation. Murine NEU1 contains 4 N-glycosylation sites, 3 of which are conserved in the human enzyme. The expression of NEU1 gives rise to differentially glycosylated proteins.

METHODS:

We generated single-point mutations in mouse NEU1 at each of the 4 N-glycosylation sites. Mutant enzymes were expressed in NEU1-deficient cells in the presence and absence of PPCA.

RESULTS:

All 4 N-glycosylation variants were targeted to the lysosomal/endosomal compartment. All N-glycans, with the exception of the most C-terminal glycan, were important for maintaining stability or catalytic activity. The loss of catalytic activity caused by the deletion of the second N-glycan was rescued by increasing PPCA expression. Similar results were obtained with a human NEU1 N-glycosylation mutant identified in a sialidosis patient. The N-terminal N-glycan of NEU1 is indispensable for its function, whereas the C-terminal N-glycan appears to be non-essential. The omission of the second N-glycan can be compensated for by upregulating the expression of PPCA.

GENERAL SIGNIFICANCE:

These findings could be relevant for the design of target therapies for patients carrying specific NEU1 mutations.

PMID:
19714866
[PubMed - indexed for MEDLINE]
PMCID:
PMC2888680
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk