Zhao X, Siu C H
Banting and Best Department of Medical Research, University of Toronto, Ontario M5G 1L6, Canada.
J Biol Chem. 1996 Mar 22;271(12):6563-6. doi: 10.1074/jbc.271.12.6563.
The cell adhesion molecule L1 plays an important role in neural development. We have previously demonstrated that the second immunoglobulin-like domain (Ig2) of L1 contains both homophilic binding and neuritogenic activities (Zhao, X., and Siu, C.-H. (1995) J. Biol. Chem. 270, 29413-29421). Recently, two mutations (R184Q and H210Q) within the Ig2 region of the human L1 gene have been shown to be responsible for X-linked hydrocephalus and the related MASA (mental retardation, aphasia, shuffling gait, and adducted thumbs) syndrome. Glutathione S-transferase-Ig2 fusion proteins containing these mutations were used to evaluate their effects on L1. The homophilic binding activity of fusion proteins and their ability to promote neurite outgrowth from retinal cells were examined. The R184Q mutation led to a complete loss of both homophilic binding and neuritogenic activities, while the H210Q mutation resulted only in a partial loss. These results provide, for the first time, direct demonstration of the deleterious effects of hydrocephalus/MASA mutations on two intrinsic properties of L1.
细胞黏附分子L1在神经发育中起重要作用。我们之前已经证明，L1的第二个免疫球蛋白样结构域（Ig2）兼具嗜同性结合和促神经突生长活性（Zhao, X., and Siu, C.-H. (1995) J. Biol. Chem. 270, 29413 - 29421）。最近，已表明人类L1基因Ig2区域内的两个突变（R184Q和H210Q）与X连锁脑积水及相关的MASA（智力迟钝、失语、拖步和拇指内收）综合征有关。含有这些突变的谷胱甘肽S-转移酶-Ig2融合蛋白被用于评估它们对L1的影响。检测了融合蛋白的嗜同性结合活性及其促进视网膜细胞神经突生长的能力。R184Q突变导致嗜同性结合和促神经突生长活性完全丧失，而H210Q突变仅导致部分丧失。这些结果首次直接证明了脑积水/MASA突变对L1两种内在特性的有害影响。
