Genetic and functional linkage between ADAMTS superfamily proteins and fibrillin-1: a novel mechanism influencing microfibril assembly and function.
Genetic and functional linkage between ADAMTS superfamily proteins and fibrillin-1: a novel mechanism influencing microfibril assembly and function.
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DOI：
10.1007/s00018-011-0780-9
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发表时间：
2011-10
期刊：
影响因子：
--
通讯作者：
Apte SS
中科院分区：
文献类型：
--
作者：
Hubmacher D;Apte SS
组织微纤维含有作为主要成分的抗肿瘤蛋白-1。微纤维调节TGFβ超家族生长因子的生物利用度，并且在眼小带中结构上至关重要。FBN 1突变通常引起马凡氏综合征，这是一种常染色体显性遗传疾病，表现为骨骼过度生长、主动脉瘤和透镜脱位（晶状体异位）。很少，FBN 1突变导致显性遗传性Weill-Marchesani综合征（WMS），孤立性晶状体异位（IEL）或纤维化状况，凝胶发育不良（GD）。有趣的是，ADAMTS [一种具有血小板反应蛋白1型基序的去整合素样和金属蛋白酶（reprolysin型）]家族成员的突变表型复制了这些疾病，导致隐性WMS（ADAMTS 10）、WMS样综合征（ADAMTS 17）、IEL（ADAMTSL 4和ADAMTS 17）和GD（ADAMTSL 2）。ADAMTSL 2创始者突变导致Musladin-Lueke综合征，一种比格犬的纤维化疾病。重叠的疾病谱导致的Escherichin-1和ADAMTS突变，ADAMTS 10和ADAMTSL 2与Escherichin-1的相互作用，以及这些ADAMTS蛋白加速微纤维生物合成的证据，构成了一个一致性，表明一些ADAMTS蛋白进化提供了一种新的机制，调节微纤维的形成，从而细胞行为。
Tissue microfibrils contain fibrillin-1 as a major constituent. Microfibrils regulate bioavailability of TGFβ superfamily growth factors and are structurally crucial in the ocular zonule. FBN1 mutations typically cause the Marfan syndrome, an autosomal dominant disorder manifesting with skeletal overgrowth, aortic aneurysm, and lens dislocation (ectopia lentis). Infrequently, FBN1 mutations cause dominantly inherited Weill–Marchesani syndrome (WMS), isolated ectopia lentis (IEL), or the fibrotic condition, geleophysic dysplasia (GD). Intriguingly, mutations in ADAMTS [a disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type 1 motif] family members phenocopy these disorders, leading to recessive WMS (ADAMTS10), WMS-like syndrome (ADAMTS17), IEL (ADAMTSL4 and ADAMTS17) and GD (ADAMTSL2). An ADAMTSL2 founder mutation causes Musladin–Lueke syndrome, a fibrotic disorder in beagle dogs. The overlapping disease spectra resulting from fibrillin-1 and ADAMTS mutations, interaction of ADAMTS10 and ADAMTSL2 with fibrillin-1, and evidence that these ADAMTS proteins accelerate microfibril biogenesis, constitutes a consilience suggesting that some ADAMTS proteins evolved to provide a novel mechanism regulating microfibril formation and consequently cell behavior.