GLOMERULAR EPITHELIAL PROTEIN 1 (GLEPP1)

描述(改编自《调查者摘要》)：机制 对肾病综合征的责任在很大程度上是未知的。足细胞是 负责维持滤过屏障的主要细胞 肾小球。肾小球滤过液在细小的 足细胞足突交错和横跨裂隙隔膜(a 修改的细胞间连接)。在肾小球损伤中 与渗漏的发展相关的足突变得模糊 过滤器的。他们寻找可能调节足细胞的分子。 足突的结构和功能，以更好地了解调节 肾小球滤过器与肾病的异常 综合症。GLEPP1是一种受体样膜蛋白酪氨酸磷酸酶 (PTPase)驻留在足细胞的足突上。GLEPP1具有 已被克隆、鉴定和测序。一种假设是，受体 调节肾小球蛋白质的过滤，并通过 它能够使脚突中的蛋白质去磷酸化，可能是那些 它们控制着缝隙横隔膜(特殊的细胞间连接) 脚部突起。毫不含糊地确立这一新的 他们将敲除GLEPP1基因，并进一步执行 GLEPP1控制肾小球机制的实验研究 渗透性。他们将分析这种受体如何向下游传递信号到它的 效应器分子。他们将确定GLEPP1的损失是否 与FSGS的肾小球预后不良有关，并将使用 GLEPP1可能是一种检测足细胞损伤的大鼠模型 是预测治疗反应和预后的有用标志物。一起， 这些分析将极大地促进我们对 肾小球滤过器受到监管，并可能提供关于如何 影响滤器的病理过程，如肾病综合征， 是可以治疗的。

DESCRIPTION (Adapted from Investigator's Abstract): The mechanisms responsible for the Nephrotic Syndrome are largely unknown. Podocytes are the major cells responsible for maintaining the filtration barrier of the renal glomerulus. The glomerular filtrate passes between the delicate interdigitating podocyte foot processes and across the slit diaphragm (a modified intercellular junction) between them. In glomerular injury these foot processes become effaced in association with development of leakiness of the filter. They searched for molecules that might regulate podocyte foot process structure and function, to better understand the regulation of the glomerular filter and the abnormalities that occur in the Nephrotic Syndrome. GLEPP1 is a receptor-like membrane protein tyrosine phosphatase (PTPase) that is resident on the foot processes of the podocyte. GLEPP1 has been cloned, characterized and sequenced. A hypothesis is that the receptor regulates the glomerular filtration of protein, and that it does so through its ability to dephosphorylate proteins in foot processes, possibly those which control the slit diaphragm (special intercellular junction) between foot processes. To unequivocally establish the importance of this new mechanism they will knock out the GLEPP1 gene, and perform further experiments to document the mechanism by which GLEPP1 controls glomerular permeability. They will analyze how this receptor signals downstream to its effector molecules. They will determine whether loss of GLEPP1 is associated with poor prognosis for the glomerulus in FSGS, and will use a rat model to examine podocyte injury with the concept that GLEPP1 may be a useful marker for predicting response to therapy and prognosis. Together, these analyses will significantly advance our understanding of how the glomerular filter is regulated, and possibly provide new insights about how pathologic processes affecting the filter, such as the Nephrotic Syndrome, can be treated.