Distinct domains of the limbic system-associated membrane protein (LAMP) mediate discrete effects on neurite outgrowth
Distinct domains of the limbic system-associated membrane protein (LAMP) mediate discrete effects on neurite outgrowth
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DOI：
10.1016/s1044-7431(03)00237-9
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发表时间：
2003-11-01
影响因子：
3.5
通讯作者：
Levitt, P
中科院分区：
文献类型：
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作者：
Eagleson, KL;Pimenta, AF;Levitt, P
边缘系统相关膜蛋白(LAMP)是一种糖基化磷脂酰肌醇锚定的糖蛋白，含有三个免疫球蛋白(Ig)结构域，可促进或抑制神经突起的生长，具体取决于所检测的神经元数量。在本研究中，我们调查了负责这些活动的领域。结构域的缺失表明，N-末端的IGI结构域是海马神经元中观察到的促进轴突活性的必要条件和充分条件。相反，抑制SCG神经元突起生长需要全长LAMP，尽管选择性地抑制第二个Ig结构域，而不是第一或第三个结构域，可阻止这种抑制效果。这表明LAMP的IgII结构域具有轴突抑制活性，但仅在全长配置的背景下。CoVasphere结合分析表明IGI/IGI相互作用，但IgII与任何其他结构域之间没有相互作用，这与每个结构域介导的生物学活性一致。这些数据表明，LAMP可能是一种双功能导向分子，具有不同的结构域，有助于促进和抑制轴突生长。(C)2003 Elsevier Inc.保留所有权利。
The limbic system-associated membrane protein (LAMP) is a glycosylphosphatidylinositol-anchored glycoprotein with three immunoglobulin (Ig) domains that can either enhance or inhibit neurite outgrowth depending upon the neuronal population examined. In the present study, we investigate the domains responsible for these activities. Domain deletion revealed that the N-terminal IgI domain is necessary and sufficient for the neurite-promoting activity observed in hippocampal neurons. In contrast, inhibition of neurite outgrowth in SCG neurons, which is mediated by heterophilic interactions, requires full-length LAMP, although selective inhibition of the second Ig domain, but not the first or third domains, prevented the inhibitory effect. This indicates that the IgII domain of LAMP harbors the neurite-inhibiting activity, but only in the context of the full-length configuration. Covasphere-binding analyses demonstrate IgI/IgI interactions, but no interaction between IgII and any other domain, consistent with the biological activities that each domain mediates. The data suggest that LAMP may serve as a bifunctional guidance molecule, with distinct structural domains contributing to the promotion and inhibition of neurite outgrowth. (C) 2003 Elsevier Inc. All rights reserved.