An essential oligomannosidic glycan chain in the catalytic domain of autotaxin, a secreted lysophospholipase-D

Silvia Jansen, Nico Callewaert, Isabelle Dewerte, Maria Andries, Hugo Ceulemans, Mathieu Bollen

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Autotaxin/NPP2, a secreted lysophospholipase-D, promotes cell proliferation, survival, and motility by generating the signaling molecule lysophosphatidic acid. Here we show that ectonucleotide pyrophosphatase/ phosphodiesterase 2 (NPP2) is N-glycosylated on Asn-53, Asn-410, and Asn-524. Mutagenesis and deglycosylation experiments revealed that only the glycosylation of Asn-524 is essential for the expression of the catalytic and motility-stimulating activities of NPP2. The N-glycan on Asn-524 was identified as Man8/9GlcNAc2, which is rarely present on mature eukaryotic glycoproteins. Additional studies show that this Asn-524-linked glycan is not accessible to α-1,2-mannosidase, suggesting that its non-reducing termini are buried inside the folded protein. Consistent with a structural role for the Asn-524-linked glycan, only the mutation of Asn-524 augmented the sensitivity of NPP2 to proteolysis and increased its mobility during Blue Native PAGE. Asn-524 is phylogenetically conserved and maps to the catalytic domain of NPP2, but a structural model of this domain suggests that Asn-524 is remote from the catalytic site. Our study defines an essential role for the Asn-524-linked glycan chain of NPP2.

Original languageEnglish
Pages (from-to)11084-11091
Number of pages8
JournalJournal of Biological Chemistry
Volume282
Issue number15
DOIs
StatePublished - Apr 13 2007
Externally publishedYes

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