N-Linked Polylactosamine Glycan Synthesis Is Regulated by Co-Expression of β3GnT2 and GCNT2

Poly-N-acetyllactosamine (PLN) is a unique glycan composed of repeating units of the common disaccharide (Gal1,4-GlcNAc1,3)(n). The expression of PLN on glycoprotein core structures minimally requires enzyme activities for 1,4-galactosyltransferase (4GalT) and 1,3-N-acetylglucosminyltransferase (3GnT). Because 4GalTs are ubiquitous in most cells, PLN expression is generally ascribed to the tissue-specific transcription of eight known 3GnT genes in mice. In the olfactory epithelium (OE), 3GnT2 regulates expression of extended PLN chains that are essential for axon guidance and neuronal survival. N-glycan branching and core composition, however, can also modulate the extent of PLN modification. Here, we show for the first time that the 1,6-branching glycosyltransferase GCNT2 (formerly known as IGnT) is expressed at high levels specifically in the OE and other sensory ganglia. Postnatally, GCNT2 is maintained in mature olfactory neurons that co-express 3GnT2 and PLN. This highly specific co-expression suggests that GCNT2 and 3GnT2 function cooperatively in PLN synthesis. In support of this, 3GnT2 and GCNT2 co-transfection in HEK293T cells results in high levels of PLN expression on the cell surface and on adenylyl cyclase 3, a major carrier of PLN glycans in the OE. These data clearly suggest that GCNT2 functions in vivo together with 3GnT2 to determine PLN levels in olfactory neurons by regulating 1,6-branches that promote PLN extension. J. Cell. Physiol. 229: 471-478, 2014. (c) 2013 Wiley Periodicals, Inc.