BASEMENT MEMBRANE BIOSYNTHESIS

目的是了解基底膜是如何在发育过程中形成的，所以 为了解其在血液中的损伤和修复奠定基础 血管和其他组织。 基底膜的一个主要成分是IV型前胶原。我们有 随后由内皮细胞和畸胎癌细胞合成，定位 它的特殊的羧基末端，并追踪它的组装到一个超分子 通过氨基末端连接的四个分子的中间体， 这是我们所描述的。我们将确定羧基末端是如何形成的 在细胞培养和组织中成对加入，以及是否有 前胶原分子之间的额外连接。我们会发现 蛋白多糖、层粘连蛋白、粘连蛋白和其他成分与 胶原蛋白支架。我们将基底膜组装与细胞联系起来。 通过研究其在胚胎器官中的形成来研究其分裂和组织生长。 基底膜普遍存在，并在发育过程中形成。 牢房单元格。我们鉴定了一种类似于IV型前胶原的前胶原 果蝇幼虫和细胞培养，并有一个基因组DNA克隆用于 它。我们将进一步表征这种蛋白质及其超分子。 联想。我们将跟踪它的合成，以及它的m-RNA， 在正常生物体中连续的发育阶段，在有条件的， 基底膜组装中的胚胎致死突变。我们已经隔离了 基底膜层粘连蛋白，具有独特的电子显微镜外观， 来自果蝇。我们制造了针对它的抗体，也针对前胶原蛋白， 还有一种蛋白多糖。所有这些污渍基底膜。我们会 确定这些材料和其他材料在开发过程中和 它们如何形成基底膜。我们也将在原代细胞中研究这一点 培养分散的胚胎，看看细胞分化是如何相关的 涉及基底膜材料的合成。 我们的结论是，有一个强烈的，共同的主题的结构 基底膜。我们对脊椎动物和无脊椎动物的平行研究 基底膜和条件性突变将有助于揭示 容易出现局部中断的装配步骤。他们将成为榜样 人类基底膜的潜在损伤。

The aim is to learn how basement membranes are made during development, so as to lay a foundation for understanding their lesions and repair in blood vessels and other tissues. A principal component of basement membranes is procollagen IV. We have followed its synthesis by endothelial and teratocarcinoma cells, located its specialized carboxyl end, and traced its assembly to a supramolecular net via an intermediate of four molecules joined through their amino ends, which we characterized. We shall determine how the carboxyl ends come to join pairwise in cell cultures and in tissues, and whether there are additional junctions between procollagen molecules. We shall find the connections of proteoglycan, laminin, entactin and other components to the collagen scaffold. We will relate basement membrane assembly to cell division and tissue growth by studying its formation in embryo organs. Basement membranes occur universally and are formed during development of cell sheets. We characterized a procollagen similar to procollagen IV in larvae and cell cultures of Drosophila, and have a genomic DNA clone for it. We shall further characterize the protein and its supramolecular associations. We shall follow its synthesis, and of its m-RNA, at successive developmental stages in normal organisms and in a conditional, embryonic lethal mutant in basement membrane assembly. We have isolated the basement membrane laminin, of unique electron microscopic appearance, from Drosophila. We made antibodies to it, and also to the procollagen, and to a proteoglycan. All these stain basement membranes. We shall determine when these and other materials are made during development and how they form basement membranes. We shall also study this in primary cell cultures of dispersed embryos and see how cell differentiation is related to the synthesis of basement membrane materials. We conclude that there is a strong, common theme to the structure of basement membranes. Our parallel studies of vertebrate and invertebrate basement membranes, and of a conditional mutation, will help to uncover assembly steps that are prone to partial disruption. They will be examples of potential lesions of human basement membranes.