Microfibril Structure Masks Fibrillin-2 in Postnatal Tissues
Microfibril Structure Masks Fibrillin-2 in Postnatal Tissues
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DOI：
10.1074/jbc.m109.087031
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发表时间：
2010-06-25
影响因子：
4.8
通讯作者：
Sakai, Lynn Y.
中科院分区：
文献类型：
--
作者：
Charbonneau, Noe L.;Jordan, C. Diana;Sakai, Lynn Y.
原纤维蛋白微纤维是存在于结缔组织中的聚合结构。微纤维蛋白和微纤维相关分子的突变引起的多种遗传疾病已经证明了微纤维蛋白对结缔组织功能的重要性。然而，微纤维结构的知识是有限的，主要是由于它们的不溶性。大多数以前的研究都集中在微纤维聚合物内的微纤维蛋白-1是如何组织的。在这项研究中，免疫化学的方法被用来规避微纤维的不溶性，以确定在出生后的微纤维结构中的作用的Replanin-2。使用具有确定表位的单克隆和多克隆抗体，从野生型和Rheumin-1空组织的研究中获得的结果表明，N-末端Rheumin-2表位在出生后的微原纤维中被掩蔽，并且可以通过酶消化或通过Fbn 1的遗传消融来揭示。从这些研究中，我们得出结论，胎儿的胎儿神经肽聚合物形成一个内部核心内出生后的微纤维和微纤维结构的发展，生长和发育进行到出生后的时期。此外，一个新的隐藏网站存在于EGF 4中的Escarin-1的文件强调了分子的复杂性和组织特异性差异的微纤维结构。
Fibrillin microfibrils are polymeric structures present in connective tissues. The importance of fibrillin microfibrils to connective tissue function has been demonstrated by the multiple genetic disorders caused by mutations in fibrillins and in microfibril-associated molecules. However, knowledge of microfibril structure is limited, largely due to their insolubility. Most previous studies have focused on how fibrillin-1 is organized within microfibril polymers. In this study, an immunochemical approach was used to circumvent the insolubility of microfibrils to determine the role of fibrillin-2 in postnatal microfibril structure. Results obtained from studies of wild type and fibrillin-1 null tissues, using monoclonal and polyclonal antibodies with defined epitopes, demonstrated that N-terminal fibrillin-2 epitopes are masked in postnatal microfibrils and can be revealed by enzymatic digestion or by genetic ablation of Fbn1. From these studies, we conclude that fetal fibrillin polymers form an inner core within postnatal microfibrils and that microfibril structure evolves as growth and development proceed into the postnatal period. Furthermore, documentation of a novel cryptic site present in EGF4 in fibrillin-1 underscores the molecular complexity and tissue-specific differences in microfibril structure.