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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."xsd:string
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http://purl.uniprot.org/citations/19714866http://purl.uniprot.org/core/author"Wang D."xsd:string
http://purl.uniprot.org/citations/19714866http://purl.uniprot.org/core/author"Taylor G."xsd:string
http://purl.uniprot.org/citations/19714866http://purl.uniprot.org/core/author"d'Azzo A."xsd:string
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http://purl.uniprot.org/citations/19714866http://purl.uniprot.org/core/author"Zaitsev S."xsd:string
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http://purl.uniprot.org/citations/19714866http://purl.uniprot.org/core/name"Biochim Biophys Acta"xsd:string
http://purl.uniprot.org/citations/19714866http://purl.uniprot.org/core/pages"275-282"xsd:string
http://purl.uniprot.org/citations/19714866http://purl.uniprot.org/core/title"Protective protein/cathepsin A rescues N-glycosylation defects in neuraminidase-1."xsd:string
http://purl.uniprot.org/citations/19714866http://purl.uniprot.org/core/volume"1790"xsd:string
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