Yanagisawa Makoto, Nakamura Kazuo, Taga Tetsuya
The 21st Century COE program Cell Fate Regulation Research and Education Unit, Kumamoto University, Honjo 2-2-1, Kumamoto 860-0811, Japan.
Genes Cells. 2004 Sep;9(9):801-9. doi: 10.1111/j.1365-2443.2004.00764.x.
Neuronal and glial cells organizing the central nervous system are generated from common neural precursor cells present in the neuroepithelium during development. We tried to clarify functions of a cell surface microdomain, lipid raft, in neuroepithelial cells (NECs). NECs are suggested to adhere to fibronectin substratum dependently on integrin molecules. We found that beta1 integrin, a component of fibronectin receptors, was distributed in lipid rafts. Methyl-beta-cyclodextrin (MBCD), an inhibitor of lipid raft formation, inhibited the integrin-fibronectin interaction-dependent adhesion of NECs. However, inhibition of synthesis of glycosphingolipids (GSL), components of lipid rafts, did not affect NEC adhesion. Leukaemia inhibitory factor (LIF), an interleukin 6 type cytokine, induces astrocyte differentiation of NECs via activation of a transcription factor STAT3. We detected gp130, JAK1 and Ras but not STAT3 and ERK2 molecules in lipid rafts of NECs. Disruption of lipid rafts by MBCD inhibited LIF-induced ERK activation but not STAT3 activation. It is thus suggested that LIF-downstream molecules have differential lipid raft-dependency in terms of activation upon LIF-stimulation. In this study, we found functions of lipid rafts in cell adhesion and signal transduction in NECs. This is the first report that characterized functions of lipid rafts in embryonic neural precursor cells.
在发育过程中，构成中枢神经系统的神经元和神经胶质细胞由神经上皮中存在的常见神经前体细胞产生。我们试图阐明神经上皮细胞（NECs）中一种细胞表面微结构域——脂筏的功能。有研究表明，NECs依赖整合素分子黏附于纤连蛋白基质。我们发现，纤连蛋白受体的一个组分β1整合素分布于脂筏中。脂筏形成抑制剂甲基-β-环糊精（MBCD）可抑制NECs依赖整合素-纤连蛋白相互作用的黏附。然而，抑制脂筏组分鞘糖脂（GSL）的合成并不影响NECs的黏附。白血病抑制因子（LIF）是一种白细胞介素6型细胞因子，它通过激活转录因子STAT3诱导NECs向星形胶质细胞分化。我们在NECs的脂筏中检测到了gp130、JAK1和Ras，但未检测到STAT3和ERK2分子。MBCD破坏脂筏可抑制LIF诱导的ERK激活，但不影响STAT3激活。因此，提示LIF下游分子在LIF刺激后的激活方面具有不同的脂筏依赖性。在本研究中，我们发现了脂筏在NECs细胞黏附和信号转导中的功能。这是首篇对胚胎神经前体细胞中脂筏功能进行表征的报道。
