Role of Pactolus in the innate immune response

描述(申请人提供)：细胞黏附的机制 由于其独特的性质，在免疫反应研究中具有特殊的意义 反应的主要成分，循环细胞。大多数器官 系统由细胞组成，这些细胞在该组织中的位置是固定的 在分化过程中。或者，免疫器官系统由以下部分组成 不断从骨髓中新衍生出来的细胞类型 并必须在身体内寻找其特定的特定部位 功能。 我们已经分离出一种新的基因，命名为Pactolus，它与 B整合素。该基因首次被分离出来是因为它在 与粘膜肥大细胞相比，成熟的结缔组织肥大细胞。 随后我们发现，动物体内的主要细胞 太子参是一种成熟的中性粒细胞。发现了Pactolus蛋白 有两种主要构型：截断和膜结合。对中性粒细胞的影响 激活时，截短形式被分泌到上清液中。另外， 激活后细胞表面蛋白质的表达也增加 这是由于细胞内储存的动员。这种蛋白质，通过 结构类比必须是一种黏附受体，从而具有结合的潜力 以细胞结合形式或可溶性形式直接与其配体结合。 这个应用程序建议定义Pactolus蛋白在 通过发展一系列方法来研究细胞和动物 通过对已有的太子参生物学的分析，分析其功能。 创造了Pactolus基因敲除动物，并加深了我们对 基因的转录控制。了解其转录调控 尤其耐人寻味，因为这种蛋白质是在不适当的细胞中产生的 (淋巴细胞等)会导致细胞死亡。通过遵循详细的实验 这个计划的应用，这个角色很有趣，也很令人惊讶 动物免疫反应中的蛋白质将被阐明

DESCRIPTION (provided by applicant): The mechanism of cell adhesion takes on special significance in studies of the immune response due to the unique nature of the primary constituents of the response, circulating cells. Most organ systems are comprised of cells whose position within that tissue is fixed during differentiation. Alternatively, the immune organ system consists of cells types that are continually being derived de novo from bone marrow precursors and must seek out selected sites within the body for their specific functions. We have isolated a novel gene, dubbed Pactolus that is related to the family of B integrins. This gene was first isolated due to its selective expression in maturing connective tissue mast cells compared to mucosal mast cells. Subsequently we have found that the major cell of the animal that produces Pactolus is the maturing and mature neutrophil. The Pactolus protein is found in two primary configurations: truncated and membrane bound. Upon neutrophil activation, the truncated form is secreted into the supernatant. Additionally, the cell surface expression of the protein is also increased after activation due to the mobilization of intracellular stores. This protein, which by structural analogy must be an adhesion receptor, thus has the potential to bind directly to its ligand with either a cell bound or soluble form. This application proposes to define the function of the Pactolus protein within the cell and the animal by developing a series of approaches to study the cell biology of Pactolus, to analyze its function via the analysis of already created Pactolus knockout animals, and to further our understanding of the transcriptional control of the gene. Understanding its transcriptional control is especially intriguing since production of the protein in inappropriate cells (lymphocytes, etc) leads to cell death. By following the detailed experimental plan of this application, the role of this very interesting and surprising protein in the immune response of the animal will be elucidated