N-Linked Polylactosamine Glycan Synthesis Is Regulated by Co-Expression of β3GnT2 and GCNT2
N-Linked Polylactosamine Glycan Synthesis Is Regulated by Co-Expression of β3GnT2 and GCNT2
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DOI：
10.1002/jcp.24467
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发表时间：
2014-04-01
影响因子：
5.6
通讯作者：
Schwarting, Gerald A.
中科院分区：
文献类型：
--
作者：
Henion, Timothy R.;Schwarting, Gerald A.
聚-N-乙酰乳糖胺（PLN）是由常见二糖（Gal 1，4-GlcNAc 1，3）（n）的重复单元组成的独特聚糖。PLN在糖蛋白核心结构上的表达最低限度地需要1，4-半乳糖基转移酶（4GalT）和1，3-N-乙酰葡糖胺基转移酶（3GnT）的酶活性。由于4GalT普遍存在于大多数细胞中，PLN表达通常归因于小鼠中8个已知3GnT基因的组织特异性转录。在嗅上皮（OE）中，3GnT 2调节对于轴突引导和神经元存活至关重要的延伸PLN链的表达。然而，N-聚糖分支和核心组成也可以调节PLN修饰的程度。在这里，我们首次表明，1，6-分支糖基转移酶GCNT 2（以前称为IGnT）在高水平表达，特别是在OE和其他感觉神经节。出生后，GCNT 2维持在共表达3GnT 2和PLN的成熟嗅觉神经元中。这种高度特异性的共表达表明GCNT 2和3GnT 2在PLN合成中协同发挥作用。为了支持这一点，HEK 293 T细胞中的3GnT 2和GCNT 2共转染导致细胞表面和腺苷酸环化酶3（OE中PLN聚糖的主要载体）上的高水平PLN表达。这些数据清楚地表明，GCNT 2与3GnT 2一起在体内起作用，以通过调节促进PLN延伸的1，6-分支来确定嗅觉神经元中的PLN水平。J.细胞。229：471-478，2014。(c)2013 Wiley Periodicals，Inc.
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.