INTRACELLULAR TRAFFICKING AND RECYCLING OF GLYCOLIPIDS

鞘糖脂（GLs）在神经系统的功能中起着重要作用。 哺乳动物细胞通过它们参与细胞-细胞和细胞-蛋白质 相互作用和作为受体功能的调节剂。 它们也是 许多导致人类疾病的微生物的受体， 在恶性细胞中作为肿瘤抗原。 虽然结构和 GL的组织分布已相当清楚，GL的控制 合成和代谢以及控制它们在细胞中表达的因子。 对细胞表面的了解很少。 据了解，细胞表面 GLs的表达是非常动态的，并且受到内部和外部的影响。 影响。 这个项目探讨了新陈代谢的一些方面， GLs的细胞内加工和细胞表面表达， 特别强调的是一种新的回收途径， 外源性和内源性GL从质膜，通过 细胞的生物合成机制，回到细胞表面。 的 最初的重点将放在恶性黑色素瘤细胞上， 初步信息已经形成。 该项目将研究 加入黑色素瘤和其他细胞类型的外源性GL的命运， GL结构对内化和加工影响及影响因素 (such作为糖基转移酶谱），其支配糖基转移酶的性质。 加工产品。 在实验上，该项目涉及合成 合适的GL类似物（主要是GM3神经节苷脂）及其放射性 类似物以及这些化合物用于分析动力学的用途， 化学计量和结构方面的细胞处理。 的 假设GLs通过特定的细胞表面受体与细胞结合 也将被审查。 此外，关于是否 内源性质膜GL也经历类似的再循环， 研究了 这些实验将提供以下信息： GL在细胞中再循环的程度和性质以及 涉及的机制。 它们将有助于更好地了解GL 哺乳动物细胞中的代谢和影响其细胞的因素 表面表达和功能。

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.