Xenopus ADAM 13 is a metalloprotease required for cranial neural crest-cell migration
Xenopus ADAM 13 is a metalloprotease required for cranial neural crest-cell migration
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DOI：
10.1016/s0960-9822(01)00263-9
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发表时间：
2001-06-26
期刊：
影响因子：
9.2
通讯作者：
DeSimone, DW
中科院分区：
文献类型：
--
作者：
Alfandari, D;Cousin, H;DeSimone, DW
背景：颅神经嵴（CNC）细胞起源于前神经上皮的侧缘，并迁移形成外周神经系统的部分结构、面部的肌肉、软骨和骨骼。神经嵴细胞的迁移涉及与周围神经上皮的黏附丧失以及与迁移路径中存在的细胞外基质（ECM）的细胞黏附相应增加。虽然蛋白水解活性可能有助于调节神经嵴细胞的黏附和迁移，但神经嵴特异性蛋白酶在这些过程中的作用尚未得到证实。我们先前表明，CNC细胞表达ADAM13，一种细胞表面金属蛋白酶/解聚素。已知该家族的蛋白质在细胞 - 细胞黏附和作为脱落酶方面起作用。也有人提出ADAMs可降解ECM，但这尚未在生理环境中得到证实。
结果：利用组织移植技术，我们发现过度表达野生型ADAM13的非洲爪蟾CNC细胞沿着正常CNC细胞所使用的相同的舌骨、鳃弓和下颌途径迁移。相反，表达蛋白酶缺陷型ADAM13的CNC细胞移植物无法沿着舌骨和鳃弓途径迁移。此外，野生型ADAM13的异位表达导致胚胎出现功能获得性表型，即躯干部神经嵴细胞的异常定位。我们进一步表明，表达野生型（而非蛋白酶缺陷型）ADAM13的外植胚胎组织显示细胞 - 基质黏附降低。纯化的ADAM13能够切割纤连蛋白，并且表达野生型（而非蛋白酶缺陷型）ADAM13的组织培养细胞能够重塑纤连蛋白底物。
结论：我们的研究结果支持以下假设：ADAM13的蛋白酶活性在神经嵴细胞沿特定途径迁移中起关键作用。我们提出，依赖于ADAM13对ECM和/或其他导向分子的修饰是CNC定向迁移的关键步骤。（C）2001爱思唯尔科学有限公司。保留所有权利。
Background: Cranial neural-crest (CNC) cells originate from the lateral edge of the anterior neuroepithelium and migrate to form parts of the peripheral nervous system, muscles, cartilage, and bones of the face. Neural crest-cell migration involves the loss of adhesion from the surrounding neuroepithelium and a corresponding increase in cell adhesion to the extracellular matrix (ECM) present in migratory pathways. While proteolytic activity is likely to contribute to the regulation of neural crest-cell adhesion and migration, the role of a neural crest-specific protease in these processes has yet to be demonstrated. We previously showed that CNC cells express ADAM 13, a cell surface metalloprotease/disintegrin. Proteins of this family are known to act in cell-cell adhesion and as sheddases. ADAMs have also been proposed to degrade the ECM, but this has not yet been shown in a physiological context.Results: Using a tissue transplantation technique, we show that Xenopus CNC cells overexpressing wild-type ADAM 13 migrate along the same hyoid, branchial, and mandibular pathways used by normal CNC cells. In contrast, CNC cell grafts that express protease-defective ADAM 13 fail to migrate along the hyoid and branchial pathways. In addition, ectopic expression of wild-type ADAM 13 results in a gain-of-function phenotype in embryos, namely the abnormal positioning of trunk neural-crest cells. We further show that explanted embryonic tissues expressing wild-type, but not protease-defective, ADAM 13 display decreased cell-matrix adhesion. Purified ADAM 13 can cleave fibronectin, and tissue culture cells that express wild-type, but not protease-defective, ADAM 13 can remodel a fibronectin substrate.Conclusions: Our findings support the hypothesis that the protease activity of ADAM 13 plays a critical role in neural crest-cell migration along defined pathways. We propose that the ADAM 13-dependent modification of ECM and/or other guidance molecules is a key step in the directed migration of the CNC. (C) 2001 Elsevier Science Ltd. All rights reserved.