INTRACELLULAR TRAFFICKING AND RECYCLING OF GLYCOLIPIDS

神经鞘糖脂(GLS)在血管内皮细胞的功能中起着重要作用 哺乳动物细胞通过参与细胞-细胞和细胞-蛋白质 相互作用和作为受体功能的调节器。它们还可用作 许多与人类疾病有关的微生物的受体，可以 在恶性细胞中作为肿瘤抗原。尽管这些结构和 GLS的组织分布非常清楚，GL的控制 合成和代谢及其在细胞中表达的调控因素 人们对细胞表面知之甚少。众所周知，细胞表面 GLS的表达是动态的，受内部和外部的影响 影响。这个项目探索了新陈代谢的某些方面， GLS的细胞内加工和细胞表面表达 涉及的机理。特别强调的是一种新的回收途径 外源和内源GLS从质膜，通过 细胞的生物合成机制，回到细胞表面。这个 最初的重点将放在恶性黑色素瘤细胞上， 初步信息已经开发出来。该项目将研究 外源性GLS加入黑色素瘤和其他类型细胞的命运， 总账结构对内化加工的影响及影响因素 (如糖基转移酶图谱)，控制着 加工过的产品。在实验上，该项目涉及到合成 合适的GL类似物(主要是GM3神经节苷脂)及其放射性 类似物和使用这些化合物来分析动力学， 细胞处理它们的化学计量学和结构方面。这个 GLS通过特定细胞表面受体与细胞结合的假说 还将接受检查。此外，关于是否 内源质膜GLS也将经历类似的循环 学习。综合起来，这些实验将提供关于 细胞中GL循环的程度和性质，以及GL循环的某些方面 涉及的机制。他们将有助于更好地理解GL 哺乳动物细胞的代谢及其影响细胞的因素 表面表现和功能。

Glycosphingolipids (GLs) play important roles in the functioning of mammalian Cells through their involvement in cell-cell and cell-protein interactions and as modulators of receptor function. They also serve as receptors for many microorganisms responsible for human disease and can serve as tumor antigens in malignant cells. Although the structures and tissue distribution of GLs is quite well understood, the control of GL synthesis and metabolism and factors that govern their expression at the cell surface are poorly understood. It is known that the cell surface expression of GLs is quite dynamic and subject to internal and external influences. This project explores some aspects of the metabolism, intracellular processing and cell surface expression of GLs and the mechanisms involved.Specifically emphasized is a novel recycling pathway of exogenous and endogenous GLs from the plasma membrane, through the biosynthetic mechanisms of the cell, back to the cell surface. The initial emphasis will be on malignant melanoma cells, on which preliminary information has been developed. The project will study the fate of exogenous GLs added to melanoma and other cell types, the influence of GL structure on internalization and processing and factors (such as the glycosyltransferase profiles) that govern the nature of the processed products. Experimentally, the project involves the synthesis of suitable GL analogs (mainly of GM3 ganglioside) and their radioactive analogs and the use of these compounds to analyze the kinetic, stoichimetric and structural aspects of their processing by cells. The hypothesis that GLs bind to cells through specific cell surface receptors will also be examined. Furthermore, the question as to whether endogenous plasma membrane GLs also undergo similar recycling will be studied. Taken together these experiments will provide information on the extent and nature of GL recycling in cells and some aspects of the mechanisms involved. They will aid in a better understanding of GL metabolism in mammalian cells and factors that influence their cell surface expression and function.