Integrin and neurocan binding to L1 involves distinct Ig domains

作     者：Oleszewski, M Beer, S Katich, S Geiger, C Zeller, Y Rauch, U Altevogt, P 

作者机构：German Canc Res Ctr Tumor Immunol Programme D-69120 Heidelberg Germany Univ Lund Hosp Dept Expt Pathol S-22185 Lund Sweden 

出 版 物：《JOURNAL OF BIOLOGICAL CHEMISTRY》 (生物化学杂志)

年 卷 期：1999年第274卷第35期

页      面：24602-24610页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 

主　　题：结合部位 阳离子/代谢 硫酸软骨素蛋白聚糖类/代谢 荧光抗体技术 糖苷水解酶类/药理学 肝素/药理学 杂交瘤/代谢 免疫球蛋白类/化学 整合素类/代谢 外源凝集素类 C型 白细胞L1抗原复合物 膜糖蛋白类/遗传学 膜糖蛋白类/代谢 诱变 定点 神经组织蛋白质类/代谢 神经细胞黏附分子类/遗传学 神经细胞黏附分子类/代谢 寡肽类/化学 寡肽类/遗传学 蛋白质结合 重组蛋白质类/代谢 T淋巴细胞/代谢 动物 小鼠 

摘      要：The cell adhesion molecule L1, a 200-220-kDa type I membrane glycoprotein of the Ig superfamily, mediates many neuronal processes. Originally studied in the nervous system, L1 is expressed by hematopoietic and many epithelial cells, suggesting a more expanded role, L1 supports homophilic L1-L1 and integrin-mediated cell binding and can also bind with high affinity to the neural proteoglycan neurocan;however, the binding site is unknown. We have dissected the L1 molecule and investigated the cell binding ability of Ig domains 1 and 6. We report that RGD sites in domain 6 support alpha 5 beta 1- or alpha v beta 3-mediated integrin binding and that both RGD sites are essential. Cooperation of RGD sites with neighboring domains are necessary for alpha(5)beta(1). A T cell hybridoma and activated T cells could bind to L1 in the absence of RGDs. This binding was supported by Ig domain 1 and mediated by cell surface-exposed neurocan. Lymphoid and brain-derived neurocan were structurally similar. We also present evidence that a fusion protein of the Ig 1-like domain of L1 can bind to recombinant neurocan. Our results support the notion that L1 provides distinct cell binding sites that may serve in cell-cell or cell-matrix interactions.