ELASTIC MICROFIBRILS

描述：许多脊椎动物组织的弹性特性 主要是弹性纤维，由两个形态和 生物化学上不同的成分：(1)无定形成分 完全由蛋白质弹性蛋白组成，(2)微纤维成分 由几种蛋白质组成，其确切数量尚未确定。这个 弹性蛋白无定形成分是造成弹性的主要原因 纤维的特性；微纤维成分的功能 没有很好地定义，但它似乎在组织 纤维或在控制纤维形成方面。微纤维也出现在 几种不含弹性蛋白的组织，在这里它们可以提供 锚定或其他功能。为了扩大我们对 微纤维的结构和功能，研究人员正在继续 一项协调一致的合作努力集中在以前被称为 纤维素样蛋白(FLP)与潜在的转化生长因子-β结合 蛋白质(LTBP-2)，在他们的实验室克隆。他们 假设LTBP-2的表达在很大程度上受 LTBP-2亚型转录和表达是发育中的 以特定于组织的方式控制。他们进一步假设 LTBP-2在弹性纤维的组装过程中起着重要作用。在……里面 为了检验这些假说，他们提出：(1)分离和 描述LTBP-2的大文本形式(9.0kb)，以完成 基因的克隆，并确定控制转录的元件 基因，(2)确定组织和发育模式 表达两种形式的LTBP-2，(3)研究结合情况 LTBP-2与原弹性蛋白等微纤维的相互作用 蛋白质和转化生长因子-β，并确定LTBP-2在弹性中的作用 光纤组件。编码的LTBP-2亚型的势函数 两份不同的成绩单也将被调查。这些研究将 使用各种各样的分子生物学(克隆和测序， 转基因、蛋白质重组合成)、细胞生物学(细胞 培养，体外纤维组装)免疫学(生产 单特异性抗体、免疫组织化学和EM分析)和蛋白质 (多肽合成、测序、蛋白质-蛋白质相互作用) 方法，所有这些方法目前都在调查员的 实验室。弹性纤维是电子产品的重要组成部分 许多胎儿组织的细胞外基质，包括主要血液 血管、肺、膀胱和真皮。世界上的错乱 纤维可能在多种疾病的病理中起决定性作用。 遗传性(即马凡氏综合征)和获得性(即肺气肿) 疾病。纤维的分子结构的定义和 它们的合成和组装所涉及的机制是 了解这些错乱并设计出治疗方法。

DESCRIPTION: The elastic properties of many vertebrate tissues are due largely to elastic fibers made up of two morphologically and biochemically distinct components: (1) the amorphous component made up entirely of the protein elastin, (2) the microfibrillar component made up of several proteins, whose exact number has yet to be determined. The elastin amorphous component is largely responsible for the elastic properties of the fibers; the function of the microfibrillar component is not well defined, but it appears to have some role in organizing the fiber or in controlling fiber formation. Microfibrils also appear in several tissues which do not contain elastin and here they may serve an anchoring or other function. In order to expand our understanding of microfibrillar structure and function, the investigators are continuing a concerted collaborative effort focused on the protein previously called fibrillin-like protein (FLP) and now called latent TGF-beta-binding protein (LTBP-2) which was cloned in their laboratories. They hypothesize that expression of LTBP-2 is largely controlled by transcription and that expression of LTBP-2- isoforms is developmentally controlled in a tissue-specific manner. They further hypothesize the LTBP-2 plays an important role in the assembly of the elastic fiber. In order to test these hypotheses, they propose: (1) to isolate and characterize the large transcript form (9.0 kb) of LTBP-2, to complete the cloning of the gene, and to define elements controlling transcription of the gene, (2) to determine the tissue and developmental pattern of expression of the two forms of LTBP-2, (3) to investigate binding interactions between LTBP-2 and tropoelastin, other microfibrillar proteins and TGF-beta and to determine the role of LTBP-2 in elastic fiber assembly. The potential function of LTBP-2 isoforms encoded by the two different transcripts will also be investigated. The studies will employ a wide variety of molecular biology (cloning and sequencing, transfection, recombinant synthesis of protein), cell biology (cell culture, in vitro fiber assembly) immunologic (production of monospecific antibody, immunohistochemical and EM analyses), and protein (peptide synthesis, and sequencing, protein-protein interactions) methods, all of which are currently on-going in the investigator's laboratories. Elastic fibers are critical components of the extracellular matrix of many fetal tissues, including major blood vessels, the lung, the bladder, and the dermis. Derangements in the fibers probably play a decisive role in the pathology of a variety of heritable (i.e., Marfan's Syndrome) and acquired (i.e., emphysema) diseases. Definition of the molecular structure of the fibers and the mechanism involved in their synthesis and assembly are requisite to understanding these derangements and devising cures.