Department of Biology, University of Crete, 71409 Heraklion, Crete, Greece.
Int J Biochem Cell Biol. 2011 Apr;43(4):487-95. doi: 10.1016/j.biocel.2010.12.016. Epub 2010 Dec 21.
Basement membranes constitute architecturally complex extracellular matrix (ECM) protein networks of great structural and regulatory importance. Recently, a novel group of basement membrane proteins, Fras1 (Fraser syndrome protein (1) and the Fras1-related extracellular matrix proteins Frem1, Frem2 and Frem3, has emerged. They comprise components of the sublamina densa region and contribute to embryonic epithelial-mesenchymal integrity. Fras1/Frem share common polypeptide repetitive motifs with possible interactive and organizing functions. Mutations in genes encoding Fras1, Frem1 and Frem2 are causative for dermal-epidermal detachment in the plane of sublamina densa and have been identified in different classes of mouse bleb mutants, the murine model of human Fraser syndrome, the hallmark phenotypic characteristics of which are embryonic skin blistering, cryptophthalmos and renal agenesis. Indeed, defects in FRAS1 and FREM2 have been identified in Fraser syndrome patients. The phenotypic similarity of mouse bleb mutant strains can be attributed to the fact that Fras1, Frem1 and Frem2 have been experimentally shown to interact, forming a mutually stabilized protein complex, while Frem3, which has not yet been associated with any of the existing known mutations, operates in a more independent fashion. Fras1/Frem have been recently proposed to compensate for the activity of collagen VII, a major anchoring component of the sublamina densa, the levels of which rise only during late embryonic life. By focusing on the aforementioned data, in this review we will summarize the current knowledge about Fraser syndrome proteins and describe their contribution to basement membrane biology.
基底层由具有重要结构和调节作用的架构复杂的细胞外基质 (ECM) 蛋白网络构成。最近，一类新的基底层蛋白，即 Fraser 综合征蛋白 1 (Fras1) 和 Fras1 相关的细胞外基质蛋白 Frem1、Frem2 和 Frem3，逐渐受到关注。它们是亚基底层致密区的组成部分，有助于胚胎上皮-间充质的完整性。Fras1/Frem 与可能具有相互作用和组织功能的常见多肽重复基序共享。编码 Fras1、Frem1 和 Frem2 的基因突变是亚基底层致密区平面上皮肤-表皮分离的原因，并在不同类型的小鼠水疱突变体中被发现，这些突变体是人类 Fraser 综合征的鼠模型，其显著的表型特征是胚胎皮肤水疱、cryptophthalmos 和肾发育不全。事实上，Fraser 综合征患者中已发现 FRAS1 和 FREM2 的缺陷。小鼠水疱突变体的表型相似可归因于以下事实：Fras1、Frem1 和 Frem2 已被实验证明相互作用，形成相互稳定的蛋白复合物，而 Frem3 尚未与任何已知突变相关联，因此以更独立的方式发挥作用。最近有人提出，Fras1/Frem 可补偿亚基底层主要锚定成分胶原 VII 的活性，胶原 VII 的水平仅在胚胎后期才升高。通过关注上述数据，在这篇综述中，我们将总结 Fraser 综合征蛋白的现有知识，并描述它们对基底层生物学的贡献。
