Vallejo Y, Hortsch M, Dubreuil R R
Committee on Cell Physiology and the Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, Illinois 60637, USA.
J Biol Chem. 1997 May 2;272(18):12244-7. doi: 10.1074/jbc.272.18.12244.
Members of the L1 family of homophilic neural cell adhesion molecules are thought to play an important role in nervous system development and function. It is also suggested that L1 is a direct target of ethanol in fetal alcohol syndrome, since ethanol inhibits the aggregation of cultured cells expressing L1 (Ramanathan, R., Wilkemeyer, M. F., Mittel, B., Perides, G., and Charness, M. E. (1996) J. Cell Biol. 133, 381-390). If ethanol acts directly on the homophilic adhesive function of the L1 molecule, then inhibition of aggregation by ethanol should be observed in any cell type that expresses L1. Here we examined the effect of physiologically relevant concentrations of ethanol on the aggregation of Drosophila S2 cells that expressed either neuroglian (the Drosophila homolog of L1) or human L1. The aggregation of these S2 cells is known to be solely dependent on the homophilic interactions between L1 or neuroglian molecules. Neither cell adhesion molecule was affected when cell aggregation assays were carried out in the presence of >/=38 mM ethanol. The recruitment of membrane skeleton assembly at sites of cell-cell contact (a transmembrane signaling function of human L1) was also unaffected by the presence of ethanol. Thus the previously described inhibition of cell adhesion by ethanol in L1-expressing cells cannot be explained by a simple direct effect on the adhesive activity of L1 family members.
同嗜性神经细胞粘附分子L1家族的成员被认为在神经系统发育和功能中发挥重要作用。也有研究表明,L1是胎儿酒精综合征中乙醇的直接作用靶点,因为乙醇会抑制表达L1的培养细胞的聚集(Ramanathan, R., Wilkemeyer, M. F., Mittel, B., Perides, G., and Charness, M. E. (1996) J. Cell Biol. 133, 381 - 390)。如果乙醇直接作用于L1分子的同嗜性粘附功能,那么在任何表达L1的细胞类型中都应该观察到乙醇对聚集的抑制作用。在这里,我们研究了生理相关浓度的乙醇对表达神经胶质蛋白(果蝇L1的同源物)或人L1的果蝇S2细胞聚集的影响。已知这些S2细胞的聚集完全依赖于L1或神经胶质蛋白分子之间的同嗜性相互作用。当在≥38 mM乙醇存在的情况下进行细胞聚集试验时,两种细胞粘附分子均未受到影响。乙醇的存在对细胞 - 细胞接触部位膜骨架组装的募集(人L1的一种跨膜信号功能)也没有影响。因此,先前描述的乙醇对表达L1的细胞中细胞粘附的抑制作用不能用对L1家族成员粘附活性的简单直接作用来解释。