Biosynthesis and biological function of sulfoglycolipids.-猫眼课题宝

DOI：

10.2183/pjab.89.129

发表时间：

2013

期刊：

Proceedings of the Japan Academy. Series B, Physical and biological sciences

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

Honke K

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669731/?report=classic

硫酸化赋予糖脂负电荷，并且所连接的硫酸酯基团呈现分子相互作用的部分决定因素。哺乳动物硫代糖脂由两个主要成员组成，硫苷脂（SO 3 - 3Gal-神经酰胺）和胆固醇脂（SO 3 - 3Gal-烷基酰基甘油）。硫苷脂在髓鞘中含量丰富，而硫苷脂是生精细胞所特有的。硫苷脂和胆固醇脂的碳水化合物部分通过由常见酶催化的连续反应生物合成：神经酰胺半乳糖基转移酶（CGT）和糖苷磺基转移酶（CST）。为了阐明磺基糖脂的生物学功能，我们纯化了CST，克隆了CST基因，并产生了CST基因敲除小鼠。CST基因敲除小鼠全身完全缺乏磺基糖脂。CST基因敲除小鼠表现出髓鞘功能障碍、少突胶质细胞终末分化异常增强和精子发生停滞等神经系统疾病。CST缺乏可改善肾间质炎症中L-选择素依赖的单核细胞浸润，表明硫苷脂是L-选择素的内源性配体。对磺基糖脂所必需的生物事件的分子机制的研究正在进行中。

Sulfation confers negative charge on glycolipids and the attached sulfate group presents a part of determinants for the molecular interactions. Mammalian sulfoglycolipids are comprised of two major members, sulfatide (SO3-3Gal-ceramide) and seminolipid (SO3-3Gal-alkylacylglycerol). Sulfatide is abundant in the myelin sheath and seminolipid is unique to the spermatogenic cells. The carbohydrate moiety of sulfatide and seminolipid is biosynthesized via sequential reactions catalyzed by common enzymes: ceramide galactosyltransferase (CGT) and cerebroside sulfotransferase (CST). To elucidate the biological function of sulfoglycolipids, we have purified CST, cloned the CST gene, and generated CST-knockout mice. CST-null mice completely lack sulfoglycolipids all over the body. CST-null mice manifest some neurological disorders due to myelin dysfunction, an aberrant enhancement of oligodendrocyte terminal differentiation, and an arrest of spermatogenesis. CST-deficiency ameliorates L-selectin-dependent monocyte infiltration in the renal interstitial inflammation, indicating that sulfatide is an endogenous ligand of L-selectin. Studies on the molecular mechanisms underlying the biological events for which sulfoglycolipids are essential are ongoing.