Glycosphingolipids in the regulation of the nervous system.
Glycosphingolipids in the regulation of the nervous system.
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DOI：
10.1007/978-1-4939-1154-7_14
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发表时间：
2014-01-01
影响因子：
--
通讯作者：
Furukawa, Keiko
中科院分区：
文献类型：
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作者：
Furukawa, Koichi;Ohmi, Yusuke;Furukawa, Keiko
神经节苷脂，含唾液酸的鞘糖脂（GSL）的最高表达，发现在脊椎动物的神经组织。神经节苷脂在神经组织发育过程中的变化表明它们参与神经发生和突触发生的调节。它们独特的分布模式支持它们参与神经细胞的分化和功能的建议。除了使用生物化学、组织病理学和细胞生物学方法进行的GSL研究结果之外，糖基转移酶基因的基因工程的最新进展导致了关于其在神经系统中的作用的新发现和概念。GSL在膜微区（如脂筏）中调节决定细胞命运的信号传导中的作用已被广泛研究。特别是，小鼠中糖基转移酶的基因靶向已经能够研究GSL的体内功能。敲除（KO）小鼠表现出的大多数异常表型可能反映了异常的结构和由此产生的由其GSL组成的改变引起的脂筏功能的改变。一般来说，在大多数KO小鼠中发现的异常表型比预期的要温和，这表明剩余的GSL补偿了那些丧失的功能。还有一些功能不能被其余的GSL取代。因此，GSL的功能可能有两种模式：一种是非特异性的，可以由多个GSL执行，第二种模式是缺失的GSL的功能不能由其他GSL补偿。鉴定单个GSL的天然配体对于阐明每个结构的功能至关重要。
The highest expression of gangliosides, sialic acid-containing glycosphingolipids (GSLs), is found in the nervous tissue of vertebrates. Changes in the profiles of gangliosides during the development of nervous tissues indicate that they are involved in the regulation of neurogenesis and synaptogenesis. Their distinct distribution patterns support the suggestion that they are involved in both the differentiation and function of neural cells. In addition to results of studies of GSLs done using biochemical, histopathological, and cell biological approaches, recent progress in the genetic engineering of glycosyltransferase genes has resulted in novel findings and concepts about their roles in the nervous system. Roles of GSLs in the regulation of signaling that determine cell fates in membrane microdomains such as lipid rafts have been extensively studied. In particular, gene targeting of glycosyltransferases in mice has enabled investigation of the in vivo functions of GSLs. The majority of abnormal phenotypes exhibited by knockout (KO) mice may reflect an abnormal structure and a resultant altered function of lipid rafts caused by alterations in their GSL composition. Generally speaking, abnormal phenotypes found in most KO mice were milder than expected, suggesting that the remaining GSLs compensate for the functions of those lost. There are also functions that cannot be replaced by the remaining GSLs. Thus, there may be two modes of function of GSLs: one is nonspecific and can be carried out by multiple GSLs, the second mode is that in which the function of the missing GSL(s) cannot be compensated by others. Identification of natural ligands for individual GSLs is crucial in order to clarify the functions of each structure.