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Abstract：
The laminins (LM) are a family of basement membranes glycoproteins with essential structural roles in supporting epithelia, endothelia, nerves and muscle adhesion, and signaling roles in regulating cell migration, proliferation, stem cell maintenance and differentiation. Laminins are obligate heterotrimers comprised of α, β and γ chains that assemble intracellularly. However, extracellularly these heterotrimers then assemble into higher-order networks via interaction between their laminin N-terminal (LN) domains. In vitro protein studies have identified assembly kinetics and the structural motifs involved in binding of adjacent LN domains. The physiological importance of these interactions has been identified through the study of pathogenic point mutations in LN domains that lead to syndromic disorders presenting with phenotypes dependent on which laminin gene is mutated. Genotype-phenotype comparison between knockout and LN domain missense mutations of the same laminin allows inferences to be drawn about the roles of laminin network assembly in terms of tissue function. In this review, we will discuss these comparisons in terms of laminin disorders, and the therapeutic options that understanding these processes have allowed. We will also discuss recent findings of non-laminin mediators of laminin network assembly and their implications in terms of basement membrane structure and function.
摘要：
层粘连蛋白（LM）是基底膜糖蛋白家族，在支持上皮中具有重要的结构作用，内皮,神经和肌肉粘连，以及在调节细胞迁移中的信号作用，扩散,干细胞维持和分化。层粘连蛋白是由α，胞内组装的β和γ链。然而,然后在细胞外，这些异源三聚体通过它们的层粘连蛋白N端（LN）结构域之间的相互作用组装成更高级的网络。体外蛋白质研究已经鉴定了组装动力学和参与相邻LN结构域结合的结构基序。通过研究LN结构域中的致病点突变，已经确定了这些相互作用的生理重要性，这些突变导致表现出依赖于层粘连蛋白基因突变的表型的综合征。相同层粘连蛋白的敲除和LN结构域错义突变之间的基因型-表型比较允许得出关于层粘连蛋白网络组装在组织功能方面的作用的推论。在这次审查中,我们将讨论层粘连蛋白疾病的比较，以及理解这些过程所允许的治疗选择。我们还将讨论层粘连蛋白网络组装的非层粘连蛋白介体的最新发现及其在基底膜结构和功能方面的意义。
