The fourth immunoglobulin-like domain of NCAM contains a carbohydrate recognition domain for oligomannosidic glycans implicated in association with L1 and neurite outgrowth.
The fourth immunoglobulin-like domain of NCAM contains a carbohydrate recognition domain for oligomannosidic glycans implicated in association with L1 and neurite outgrowth.
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DOI：
10.1083/jcb.121.6.1409
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发表时间：
1993-06
期刊：
影响因子：
--
通讯作者：
Schmitz B
中科院分区：
文献类型：
--
作者：
Horstkorte R;Schachner M;Magyar JP;Vorherr T;Schmitz B
我们之前已经证明，神经粘附分子L1和NCAM相互作用形成一个复合物，它与L1的结合比L1单独与L1的结合更强烈（Kadmon， G., a. Kowitz， P. Altevogt, and M. Schachner, 1990）。[j] .细胞生物学杂志。110:193-208。L1和NCAM之间的这种顺式关联是碳水化合物依赖性的（Kadmon， G.， A. Kowitz， P. Altevogt, and M. Schachner, 1990）。[j] .细胞生物学杂志。在本研究中，我们报道了L1和NCAM通过L1表达的低寡糖碳水化合物相互结合，而不是通过NCAM，如几个实验所示：(a) L1和NCAM之间的复合物形成被低寡糖碳水化合物和低聚糖本身的单抗抑制；(b) NCAM与低寡糖碳水化合物结合；(c)在L1/NCAM复合物中，低寡糖碳水化合物是隐藏的，对低寡糖碳水化合物的单克隆抗体是不可及的；(d)含有免疫球蛋白样结构域的NCAM重组蛋白片段与低寡糖聚糖结合，而不是含有纤维连接蛋白III型同源重复序列的片段。此外，NCAM的第四个免疫球蛋白样结构域与动物c型凝集素的碳水化合物识别结构域序列同源，令人惊讶的是，它也与植物凝集素序列同源。在NCAM的第四个免疫球蛋白样结构域，包含c型凝集素一致序列的一部分的肽干扰L1和NCAM之间的关联。细胞表面寡糖聚糖的功能重要性在体外神经突生长中得到了证明。当用层粘连蛋白或聚l -赖氨酸维持出生后早期小鼠小脑神经元时，低聚寡糖聚糖、糖肽、糖蛋白或含有低聚寡糖聚糖的新糖脂会抑制神经突的生长，但不受低聚寡糖或低聚寡糖衍生物的抑制。神经突的生长也被包含NCAM第四个免疫球蛋白样结构域C型凝集素一致序列部分的肽抑制。综合结果表明，碳水化合物介导的细胞表面粘附分子之间的顺式结合调节了它们的功能特性。
We have previously shown that the neural adhesion molecules L1 and NCAM interact with each other to form a complex which binds more avidly to L1 than L1 to L1 alone (Kadmon, G., A. Kowitz, P. Altevogt, and M. Schachner. 1990a. J. Cell Biol. 110:193-208). This cis-association between L1 and NCAM is carbohydrate-dependent (Kadmon, G., A. Kowitz, P. Altevogt, and M. Schachner. 1990b. J. Cell Biol. 110:209-218). In the present study, we report that L1 and NCAM bind to each other via oligomannosidic carbohydrates expressed by L1, but not by NCAM, as shown in several experiments: (a) complex formation between L1 and NCAM is inhibited by a mAb to oligomannosidic carbohydrates and by the oligosaccharides themselves; (b) NCAM binds to oligomannosidic carbohydrates; (c) within the L1/NCAM complex, the oligomannosidic carbohydrates are hidden from accessibility to a mAb against oligomannosidic carbohydrates; (d) the recombinant protein fragment of NCAM containing the immunoglobulin-like domains and not the fragment containing the fibronectin type III homologous repeats binds to oligomannosidic glycans. Furthermore, the fourth immunoglobulin-like domain of NCAM shows sequence homology with carbohydrate recognition domains of animal C-type lectins and, surprisingly, also with plant lectins. A peptide comprising part of the C-type lectin consensus sequence in the fourth immunoglobulin-like domain of NCAM interferes with the association between L1 and NCAM. The functional importance of oligomannosidic glycans at the cell surface was shown for neurite outgrowth in vitro. When neurons from early postnatal mouse cerebellum were maintained on laminin or poly-L-lysine, neurite outgrowth was inhibited by oligomannosidic glycans, by glycopeptides, glycoproteins, or neoglycolipids containing oligomannosidic glycans, but not by nonrelated oligosaccharides or oligosaccharide derivates. Neurite outgrowth was also inhibited by the peptide comprising part of the C- type lectin consensus sequence in the fourth immunoglobulin-like domain of NCAM. The combined results suggest that carbohydrate-mediated cis- associations between adhesion molecules at the cell surface modulate their functional properties.