Integrin structure
Integrin structure
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DOI：
10.1042/0300-5127:0280311
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发表时间：
2000-08-01
影响因子：
3.9
通讯作者：
Humphries, MJ
中科院分区：
文献类型：
--
作者：
Humphries, MJ
整合素是一类α， β异二聚体受体，介导细胞外粘附分子和细胞内肌动蛋白细胞骨架之间的动态联系。所有多细胞动物都表达整合素，但其多样性在物种之间差异很大；例如，在哺乳动物中，19个α和8个β亚基基因编码多肽，这些多肽结合起来形成25种不同的受体，而果蝇和隐杆线虫的基因组分别只编码5个和2个整合素a亚基。在过去的二十年里，成千上万的研究已经调查了整合素功能的分子、细胞和有机体基础。基因缺失已被证明对几乎所有整合素都起着至关重要的作用，这些缺陷表明在维持组织完整性和促进细胞迁移方面都有广泛的贡献。整合素-配体相互作用现在被认为为细胞提供物理支持，以维持内聚，允许产生牵引力以实现运动，并组织信号复合物来调节分化和细胞命运。动物模型研究也表明，整合素有助于许多常见疾病的进展，并暗示它们是潜在的治疗靶点。抗整合素单克隆抗体和拟配体肽的使用证实了这一建议在炎症、肿瘤、创伤和感染性疾病中的应用。因此，为了更多地了解组织组织和细胞运输的机制，并确定在疾病中调节这些过程的方法，人们对确定整合素功能的分子基础非常感兴趣。重要的是要在一开始就说明，整合素二聚体的三级结构是未知的。因此，我们目前对整合素功能的分子基础的理解是基于大量研究的结果，这些研究采用了广泛的互补技术。
The integrins are a family of alpha,beta heterodimeric receptors that mediate dynamic linkages between extracellular adhesion molecules and the intracellular actin cytoskeleton. Integrins are expressed by all multicellular animals, but their diversity varies widely among species; for example, in mammals, 19 alpha and 8 beta subunit genes encode polypeptides that combine to form 25 different receptors, whereas the Drosophila and Caenorhabditis genomes encode only five and two integrin a subunits respectively. Thousands of studies over the last two decades have investigated the molecular, cellular and organismal basis of integrin function. Gene deletion has demonstrated essential roles for almost all integrins, with the defects suggesting widespread contributions to both the maintenance of tissue integrity and the promotion of cellular migration. Integrin-ligand interactions are now considered to provide physical support for cells in order to maintain cohesion, to permit the generation of traction forces to enable movement, and to organize signalling complexes to modulate differentiation and cell fate. Animal-model studies have also shown that integrins contribute to the progression of many common diseases, and have implicated them as potential therapeutic targets. The use of anti-integrin monoclonal antibodies and ligandmimetic peptides has validated this suggestion for inflammatory, neoplastic, traumatic and infectious conditions. Thus, to understand more about the mechanisms underlying tissue organization and cellular trafficking, and to identify approaches for regulating these processes in disease, there is intense interest in determining the molecular basis of integrin function. It is important to state at the outset that the tertiary structure of the integrin dimer is unknown. Our current understanding of the molecular basis of integrin function is therefore compiled from the results of a large number of studies that have employed a wide range of complementary technologies.