Baboval T, Henion T, Kinnally E, Smith F I
Biomedical Sciences Department, E.K. Shriver Center, Waltham, Massachusetts 02452, USA.
J Neurosci Res. 2000 Oct 15;62(2):206-15. doi: 10.1002/1097-4547(20001015)62:2<206::AID-JNR5>3.0.CO;2-E.
Fucosylated glycoconjugates play an essential role in central nervous system development, but the regulation of expression of these molecules is not well understood. The final biosynthetic step for a major group of cerebellar fucosylated glycoconjugates (those bearing the developmentally regulated epitope 3-fucosyl-N-acetyllactosamine, CD15, and related fucosylated epitopes) is catalyzed by an alpha-1,3-fucosyltransferase (FucT). The major FucT activity in postnatal rat cerebellum has a specificity consistent with that encoded by either a Fuc-TIV- or Fuc-TIX-like gene, and thus the expression of these genes was investigated during postnatal rat cerebellar development. A rFuc-TIX cDNA was cloned and a comparison of its enzymatic activity with rFuc-TIV revealed similar results on oligosaccharides, but strikingly higher activity on lipid acceptors, suggesting a greater role for rFuc-TIX than rFuc-TIV in the synthesis of CD15 glycolipids. rFuc-TIX mRNA levels were much higher than those of rFuc-TIV in neonatal cerebellum. Whereas rFuc-TIX mRNA levels remained relatively constant, rFuc-TIV mRNA levels declined during postnatal cerebellar development. In situ hybridization of postnatal rat cerebella also revealed different patterns of expression for these two genes. The rFuc-TIV gene was expressed predominantly in Purkinje cells and the deep cerebellar nuclei throughout postnatal development, but was expressed in granule neurons only in the neonatal, and not the adult, rat. In contrast, the rFuc-TIX gene was expressed in cells in the granule cell layers in both neonatal and in the adult rat. The potential implications of the different enzymatic activities and cell localization of rFuc-TIV and rFuc-TIX expression for the regulation of fucosylated glycoconjugates during cerebellar development are discussed.
岩藻糖基化糖缀合物在中枢神经系统发育中起着至关重要的作用，但这些分子表达的调控机制尚未完全清楚。小脑主要岩藻糖基化糖缀合物（那些带有发育调控表位3-岩藻糖基-N-乙酰乳糖胺、CD15及相关岩藻糖基化表位的糖缀合物）的最后生物合成步骤由α-1,3-岩藻糖基转移酶（FucT）催化。出生后大鼠小脑的主要FucT活性与Fuc-TIV样或Fuc-TIX样基因编码的活性一致，因此研究了这些基因在出生后大鼠小脑发育过程中的表达情况。克隆了rFuc-TIX cDNA，并将其酶活性与rFuc-TIV进行比较，结果表明，在寡糖上二者结果相似，但在脂质受体上rFuc-TIX的活性显著更高，这表明在CD15糖脂的合成中，rFuc-TIX比rFuc-TIV发挥着更重要的作用。新生小脑的rFuc-TIX mRNA水平远高于rFuc-TIV。rFuc-TIX mRNA水平相对保持恒定，而rFuc-TIV mRNA水平在出生后小脑发育过程中下降。出生后大鼠小脑的原位杂交也显示这两个基因有不同的表达模式。在出生后整个发育过程中，rFuc-TIV基因主要在浦肯野细胞和小脑深部核团中表达，但仅在新生大鼠而非成年大鼠的颗粒神经元中表达。相反，rFuc-TIX基因在新生大鼠和成年大鼠的颗粒细胞层细胞中均有表达。本文讨论了rFuc-TIV和rFuc-TIX表达的不同酶活性和细胞定位对小脑发育过程中岩藻糖基化糖缀合物调控的潜在影响。
