Tzu Julia, Marinkovich M Peter
Department of Dermatology, Program in Epithelial Biology, Stanford University, Stanford, CA 94305, USA.
Int J Biochem Cell Biol. 2008;40(2):199-214. doi: 10.1016/j.biocel.2007.07.015. Epub 2007 Aug 6.
The basement membrane is a highly intricate and organized portion of the extracellular matrix that interfaces with a variety of cell types including epithelial, endothelial, muscle, nerve, and fat cells. The laminin family of glycoproteins is a major constituent of the basement membrane. The 16 known laminin isoforms are formed from combinations of alpha, beta, and gamma chains, with each chain containing specific domains capable of interacting with cellular receptors such as integrins and other extracellular ligands. In addition to its role in the assembly and architectural integrity of the basement membrane, laminins interact with cells to influence proliferation, differentiation, adhesion, and migration, processes activated in normal and pathologic states. In vitro these functions are regulated by the post-translational modifications of the individual laminin chains. In vivo laminin knockout mouse studies have been particularly instructive in defining the function of specific laminins in mammalian development and have also highlighted its role as a key component of the basement membrane. In this review, we will define how laminin structure complements function and explore its role in both normal and pathologic processes.
基底膜是细胞外基质中高度复杂且有序的部分,它与多种细胞类型相互作用,包括上皮细胞、内皮细胞、肌肉细胞、神经细胞和脂肪细胞。层粘连蛋白家族糖蛋白是基底膜的主要成分。已知的16种层粘连蛋白异构体由α、β和γ链组合而成,每条链都含有能够与细胞受体(如整合素)和其他细胞外配体相互作用的特定结构域。除了在基底膜的组装和结构完整性方面发挥作用外,层粘连蛋白还与细胞相互作用,影响增殖、分化、黏附和迁移,这些过程在正常和病理状态下都会被激活。在体外,这些功能受单个层粘连蛋白链的翻译后修饰调控。在体内,层粘连蛋白基因敲除小鼠研究在确定特定层粘连蛋白在哺乳动物发育中的功能方面特别具有启发性,也突出了其作为基底膜关键成分的作用。在这篇综述中,我们将阐述层粘连蛋白的结构如何与其功能相辅相成,并探讨其在正常和病理过程中的作用。