GOLGI COMPLEX COMPOSITION IN POLARIZED EPITHELIAL CELLS

Glgi复合体的功能将在两个极化下进行研究 上皮细胞系。细胞系(MDCK和WIF-B)代表 两种上皮细胞(肾小管和肝细胞)的模型 不同的蛋白质和/或脂肪分选机制和/或位置 递送到特定的质膜域。高尔基情结 在这一过程中扮演着重要的角色。分拣故障 极化上皮细胞中的机械有可能导致 疾病，因为需要这些细胞的完整性来定义和 维持生物体内的生理隔间。理解 高尔基复合体在引导蛋白质和脂类代谢中的作用 功能部位有助于了解疾病 进程。 高尔基复合体至少由三个小舱组成： 堆栈，以及两侧的两个多形隔室，顺式 高尔基网络(CGN)和跨高尔基网络(TGN)。这个 脂质双分子层对高尔基体结构和功能的影响 MDCK和WIF-B细胞将被研究。分布、结构 和罕见的磷脂半溶二磷脂的生物合成 酸(富含在CGN和TGN中)将被测定，其 函数将使用微扰来处理。这个 北京地区高尔基体各亚室的神经鞘糖脂和胆固醇含量 控制单元格和在单元格中进行各种扰动后 确定的，因为这些脂质被认为在 上皮细胞的分选。此外，由于肝细胞是 据信缺乏直接的途径来传递新合成的 从高尔基体到顶端质膜的蛋白质，通过 哪些新合成的鞘磷脂被输送到根尖 将对血浆WIF-B细胞进行研究。磷脂酰肌醇 对于高尔基函数来说是很重要的，显然 有别于经典的信号转导途径。有缺陷的人 磷脂酰肌醇4，5-二磷酸-5-磷酸酶定位于高尔基体 膜最近与眼脑肾综合征有关 其中极化细胞的子集是不起作用的。 高尔基体脂类成分(包括磷脂酰肌醇4，5- 双磷酸)与MDCK细胞中潜在的蛋白质分类缺陷 缺乏5-磷酸酶的情况将被评估。

The function of the Glgi complex will be studied in two polarized epithelial cell lines. The cell lines (MDCK and WIF-B) represent models of two epithelia (kidney tubule and hepatocyte) that use a different mechanism and/or site for protein and lipid sorting for delivery to specialized plasma membrane domains. The golgi complex plays an important role in this process. Malfunction of the sorting machinery in polarized epithelial cells has the potential to cause disease, since the integrity of these cells is required to define and maintain physiological compartments in the organism. Understanding the role of the Golgi complex in directing proteins and lipids their site of function is instrumental to understanding the disease process. The Golgi complex consists of at least three subcompartments: the stacks, and two pleomorphic compartments on either side, the cis Golgi network (CGN) and the trans Golgi network (TGN). The contribution of the lipid bilayer to Golgi structure and function in MDCK and WIF-B cells will be investigate. Distribution, structure and biosynthesis of the unusual phospholipid semilysobisphosphatidc acid (enriched in the CGN and TGN) will be determined, and its function will be addressed using perturbations. The glycosphingolipid and cholesterol content of Golgi subcompartments in control cells and in cells after various perturbations will be determined, since these lipids have been postulated to have a role in sorting in epithelial cells. In addition, since hepatocytes are believed to lack a direct pathway for delivery of newly synthesized proteins from the Golgi to the apical plasma membrane, the pathway by which newly synthesized sphingolipids are delivered to the apical plasma WIF-B cells will be investigated. The phosphatidylinositols are important for Golgi function in a role that is apparently distinct fromclassic signal transduction pathways. A defective phsphatidylinositol 4,5-bisphosphate 5-phosphatase localized to Golgi membranes was recently implicated in the oculocerebrorenal syndrome of Lowe, in which a subset of polarized cells is disfunctional. Golgi lipid composition (including phosphatidylinositol 4,5- bisphosphate) and potential protein sorting defects in MDCK cells lacking the 5-phosphatase will be assessed.