Baboval Thia, Liang ShuLing, Smith Frances I
Biomedical Sciences Department, E.K. Shriver Center for Mental Retardation, Waltham, Massachusetts 02452, USA.
J Neurosci Res. 2002 Mar 1;67(5):583-94. doi: 10.1002/jnr.10149.
The glycoconjugate epitopes 3-fucosyl-N-acetyllactosamine (CD15) and sulfoglucuronylcarbohydrate (SGC) mediate cell adhesion events in several systems, and are regulated both spatially and temporally during cerebellar development. In cotransfection studies using COS-1 cells, competition between glycosyltransferases that utilize a common precursor involved in the final synthetic steps of these epitopes, can modulate epitope expression. For example, cotransfection of rat alpha1,3-fucosyltransferase IV (Fuc-TIV) and either rat glucuronic acid transferase P (GlcAT) or pig alpha1,3-galactosyltransferase (GalT) resulted in the dominance of either SGC or GalalphaGal epitope expression, respectively, with blockage of CD15 epitope expression. Viral vectors expressing these glycosyltransferases were used to determine whether competition plays a role in establishing epitope dominance in cerebellar cells, and whether overexpression of competing glycosyltransferases could be used to block epitope expression. Infection of cerebellar astrocytes with viral vectors expressing either Fuc-TIV, or Fuc-TIX, caused dramatic increases in CD15 expression in the presence of continued endogenous SGC epitope expression. Likewise, viral transduction with GalT resulted in GalalphaGal expression without affecting endogenous CD15 or SGC expression. Thus, competition between these enzymes does not appear to play a role in establishing epitope expression in astrocytes, and transduction of these enzymes does not provide a method of blocking the expression of endogenous epitopes. In contrast to what was observed for astrocytes, infection with viral vectors expressing either Fuc-T, GlcAT, or GalT did not result in significant expression of the relevant epitopes (CD15, SGC or GalalphaGal, respectively) on granule neurons. These results suggest a different complement of precursors are present in granule neurons and astrocytes, presumably due to the presence of different complements of glycosyltransferases in these cells.
糖缀合物表位3-岩藻糖基-N-乙酰乳糖胺（CD15）和磺基葡糖醛酸碳水化合物（SGC）在多个系统中介导细胞黏附事件，并且在小脑发育过程中受到时空调节。在使用COS-1细胞的共转染研究中，利用参与这些表位最终合成步骤的共同前体的糖基转移酶之间的竞争，可以调节表位表达。例如，大鼠α1,3-岩藻糖基转移酶IV（Fuc-TIV）与大鼠葡糖醛酸转移酶P（GlcAT）或猪α1,3-半乳糖基转移酶（GalT）共转染，分别导致SGC或GalαGal表位表达占主导，同时CD15表位表达受阻。表达这些糖基转移酶的病毒载体被用于确定竞争是否在小脑细胞中表位优势的建立中起作用，以及竞争性糖基转移酶的过表达是否可用于阻断表位表达。用表达Fuc-TIV或Fuc-TIX的病毒载体感染小脑星形胶质细胞，在持续存在内源性SGC表位表达的情况下，导致CD15表达显著增加。同样，用GalT进行病毒转导导致GalαGal表达，而不影响内源性CD15或SGC表达。因此，这些酶之间的竞争似乎在星形胶质细胞表位表达的建立中不起作用，并且这些酶的转导不能提供一种阻断内源性表位表达的方法。与在星形胶质细胞中观察到的情况相反，用表达Fuc-T、GlcAT或GalT的病毒载体感染颗粒神经元，并未导致相关表位（分别为CD15、SGC或GalαGal）在颗粒神经元上的显著表达。这些结果表明，颗粒神经元和星形胶质细胞中存在不同的前体补充，推测是由于这些细胞中存在不同的糖基转移酶补充。
