Critical role of evolutionarily conserved glycosylation at Asn211 in the intracellular trafficking and activity of sialyltransferase ST3Gal-II

FERNANDO M. RUGGIERO; ALDO A. VILCAES; RAMIRO IGLESIAS-BARTOLOME; JOSE L. DANIOTTI

BIOCHEMICAL JOURNAL

PORTLAND PRESS LTD

Lugar: Londres; Año: 2015 vol. 469 p. 83 - 83

0264-6021

T3Gal-II, a type II transmembrane protein, is the mainmammalian sialyltransferase responsible for GD1a and GT1bganglioside biosynthesis in brain. It contains two putative Nglycosylation sites (Asn92 and Asn211). Whereas Asn92 is onlyconserved in mammalian species, Asn211 is highly conservedin mammals, birds and fish. The present study exploresthe occupancy and relevance for intracellular trafficking andenzyme activity of these potential N-glycosylations in humanST3Gal-II. We found that ST3Gal-II distributes along the Golgicomplex, mainly in proximal compartments. By pharmacological,biochemical and site-directed mutagenesis, we observed thatST3Gal-II is mostly N-glycosylated at Asn211 and that thisco-translational modification is critical for its exit from theendoplasmic reticulum and proper Golgi localization. Theindividual N-glycosylation sites had different effects on ST3GalII enzymatic activity. Whereas the N-glycan at position Asn211seems to negatively influence the activity of th