The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
Mol Genet Metab. 2012 Dec;107(4):635-47. doi: 10.1016/j.ymgme.2012.07.023. Epub 2012 Aug 3.
Fibrillins and latent transforming growth factor β binding proteins (LTBPs) are components of the extracellular matrix of connective tissue. While fibrillins are integral to the 10nm microfibrils, and often associated with elastin, all family members are likely to have an additional role in regulating the bioavailability of transforming growth factor β (TGBβ). Both fibrillins and LTBPs are large glycoproteins, containing a series of calcium binding epidermal growth factor domains as well as a number of copies of a unique 8 cysteine domain found only in this protein superfamily. There are three mammalian fibrillins and four LTBPs. Fibrillin monomers link head to tail in microfibrils which can then form two and three dimensional structures. In some tissues elastin is recruited to the fibrillin microfibrils to provide elasticity to the tissue. LTBPs are part of the TGBβ large latent complex which sequesters TGBβ in the extracellular matrix. Fibrillin-1 appears to bind to LTBPs to assist in this process and is thus involved in regulating the bioavailability of TGBβ. Mutation of fibrillin genes results in connective tissue phenotypes which reflect both the increased level of active TGBβ and the structural failure of the extracellular matrix due to the absence or abnormality of fibrillin protein. Fibrillinopathies include Marfan syndrome, familial ectopia lentis, familial thoracic aneurysm (mutations of FBN1) and congenital contractural arachnodactyly (mutation of FBN2). There are no diseases currently associated with mutation of FBN3 in humans, and this gene is no longer active in rodents. Expression patterns of fibrillin genes are consistent with their role in extracellular matrix structure of connective tissue. FBN1 expression is high in most cell types of mesenchymal origin, particularly bone. Human and mouse FBN2 expression is high in fetal cells and has more restricted expression in mesenchymal cell types postnatally. FBN3 is expressed early in development (embryonic and fetal tissues) in humans. The fibrillins are thus important in maintaining the structure and integrity of the extracellular matrix and, in combination with their sequence family members the LTBPs, also contribute to the regulation of the TGFβ family of major growth factors.
原纤维蛋白和潜伏转化生长因子β结合蛋白（LTBPs）是结缔组织细胞外基质的组成部分。虽然原纤维蛋白是 10nm 微纤维的组成部分，通常与弹性蛋白相关，但所有家族成员都可能在调节转化生长因子β（TGBβ）的生物利用度方面发挥额外作用。原纤维蛋白和 LTBPs 都是大型糖蛋白，含有一系列钙结合表皮生长因子结构域以及仅在该蛋白超家族中发现的多个独特的 8 个半胱氨酸结构域拷贝。哺乳动物中有三种原纤维蛋白和四种 LTBPs。原纤维蛋白单体在微纤维中头尾相连，然后形成二维和三维结构。在某些组织中，弹性蛋白被招募到原纤维蛋白微纤维中，为组织提供弹性。LTBPs 是 TGBβ大潜伏复合物的一部分，将 TGBβ隔离在细胞外基质中。原纤维蛋白-1 似乎与 LTBPs 结合以协助此过程，因此参与调节 TGBβ的生物利用度。原纤维蛋白基因的突变导致结缔组织表型，这反映了活性 TGBβ水平的增加以及由于原纤维蛋白蛋白的缺失或异常导致细胞外基质的结构失败。原纤维蛋白病包括马凡综合征、家族性晶状体异位、家族性胸主动脉瘤（FBN1 突变）和先天性挛缩性蜘蛛指（FBN2 突变）。目前没有与人类 FBN3 突变相关的疾病，并且该基因在啮齿动物中不再活跃。原纤维蛋白基因的表达模式与其在结缔组织细胞外基质结构中的作用一致。FBN1 在大多数间充质来源的细胞类型中表达较高，特别是在骨骼中。人类和小鼠 FBN2 在胎儿细胞中表达较高，在出生后间充质细胞类型中的表达更为受限。FBN3 在人类发育早期（胚胎和胎儿组织）表达。原纤维蛋白对于维持细胞外基质的结构和完整性非常重要，并且与它们的序列家族成员 LTBPs 一起，也有助于调节 TGFβ 家族的主要生长因子。
