Mechanism of homophilic binding mediated by ninjurin, a novel widely expressed adhesion molecule
Mechanism of homophilic binding mediated by ninjurin, a novel widely expressed adhesion molecule
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DOI：
10.1074/jbc.272.34.21373
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发表时间：
1997-08-22
影响因子：
4.8
通讯作者：
Milbrandt, J
中科院分区：
文献类型：
--
作者：
Araki, T;Zimonjic, DB;Milbrandt, J
Ninjurin是一种新的蛋白，在神经损伤后，在背根神经节（DRG）神经元和雪旺细胞中都被上调。我们之前报道过，Ninjurin显示了一种亲同质粘附分子的特性，并促进原代培养的DRG神经元的神经突生长。我们现在发现，Ninjurin在成人和胚胎组织中都广泛表达，主要是在上皮细胞中。通过诱变和使用合成的寡肽作为ninjurin介导的粘附的竞争性抑制剂，ninjurin介导的亲同型粘附的关键结构域定位在ii -残基区域（Pro（26）和Asn（37）之间），特别重要的是29号位置的Trp残基和该区域的3个精氨酸。我们发现，抑制表达ninjurin的Jurkat细胞聚集的肽也能够阻断ninjurin促进DRG神经元神经突延伸的能力。通过FISH分析，ninjurin基因定位在人类染色体9q22上。一些病因不明的遗传疾病已被定位到这一区域，包括遗传性感觉神经病变1型、自愈性鳞状上皮瘤、手足裂型畸形1型和家族性扩张性心肌病。
Ninjurin is a novel protein that is up-regulated after nerve injury both in dorsal root ganglion (DRG) neurons and in Schwann cells, We previously reported that ninjurin demonstrates properties of a homophilic adhesion molecule and promotes neurite outgrowth from primary cultured DRG neurons, We have now found that ninjurin is widely expressed in both adult and embryonic tissues, primarily in those of epithelial origin, Aggregation assays were used to demonstrate that ninjurin-mediated adhesion requires divalent cations and is an energy-dependent process, The critical domain for ninjurin-mediated homophilic adhesion was localized to an Ii-residue region (between Pro(26) and Asn(37)) by mutagenesis and by employing synthetic oligopeptides as competitive inhibitors of ninjurin-mediated adhesion, Of particular importance are the Trp residue at position 29 and the 3 arginines in the region, Furthermore, we show that the peptide which inhibits aggregation of Jurkat cells expressing ninjurin is also capable of blocking the ability of ninjurin to promote neurite extension from DRG neurons, Using FISH analysis, the ninjurin gene was localized to human chromosome 9q22. Several genetic diseases of unknown etiology have been mapped to this region, including hereditary sensory neuropathy type 1, self-healing squamous epithelioma, split-hand/foot deformity type 1, and familial dilated cardiomyopathy.