IDENTIFICATION OF THE BORDER BETWEEN FIBRONECTIN TYPE-III HOMOLOGOUS REPEAT-2 AND REPEAT-3 OF THE NEURAL CELL-ADHESION MOLECULE L1 AS A NEURITE OUTGROWTH-PROMOTING AND SIGNAL-TRANSDUCING DOMAIN

IDENTIFICATION OF THE BORDER BETWEEN FIBRONECTIN TYPE-III HOMOLOGOUS REPEAT-2 AND REPEAT-3 OF THE NEURAL CELL-ADHESION MOLECULE L1 AS A NEURITE OUTGROWTH-PROMOTING AND SIGNAL-TRANSDUCING DOMAIN
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DOI:
10.1002/neu.480280304
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发表时间:
1995-11-01
期刊:
JOURNAL OF NEUROBIOLOGY
影响因子:
--
通讯作者:
SCHACHNER, M
SCHACHNER, M
中科院分区:
其他
文献类型:
--
作者:
APPEL, F;HOLM, J;SCHACHNER, M

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为了确定神经细胞粘附分子L1参与神经突生长的领域,我们已经产生了单克隆抗体L1和研究其对小脑小神经元的神经突生长的影响在文化。当将10种抗体包被为底物时,只有抗体557.B6(其识别由在纤连蛋白III型同源重复序列2和3之间的边界处包含氨基酸818至832的合成肽表示的表位)在促进神经突生长、增加细胞内Ca2+水平和刺激肌醇磷酸的周转方面与L1一样有效,这些发现表明,神经突生长和这些第二信使的变化是相关的。通过Ca 2+通道拮抗剂和百日咳毒素抑制L1和抗体557.B6上神经突生长的能力证实了这种相关性。这些观察结果表明,第一次一个独特的网站上的细胞表面结合L1作为一个突出的信号转导域,通过它的识别事件似乎是漏斗状的触发神经突生长,增加营业额的肌醇磷酸,并提高细胞内的Ca2+水平。(C)John Wiley & Sons,Inc.
To determine the domains of the neural cell adhesion molecule L1 involved in neurite outgrowth, we have generated monoclonal antibodies against L1 and investigated their effects on neurite outgrowth of small cerebellar neurons in culture. When the 10 antibodies were coated as substrate, only antibody 557.B6, which recognizes an epitope represented by a synthetic peptide comprising amino acids 818 to 832 at the border between the fibronectin type III homologous repeats 2 and 3, was as efficacious as L1 in promoting neurite outgrowth, increasing intracellular levels of Ca2+, and stimulating the turnover of inositol phosphates, These findings suggest that neurite outgrowth and changes in these second messengers are correlated. Such a correlation was confirmed by the ability of Ca2+ channel antagonists and pertussis toxin to inhibit neurite outgrowth on L1 and antibody 557.B6. These observations indicate for the first time a distinct site on cell surface-bound L1 as a prominent signal-transducing domain through which the recognition events appear to be funneled to trigger neurite outgrowth, increase turnover of inositol phosphates, and elevate intracellular levels of Ca2+. (C) 1995 John Wiley & Sons, Inc.