GLYCOLIPID PROTEIN ANCHORS IN PNH AND THY-1 MUTANTS

通过糖磷脂锚定的质膜蛋白是 对许多新陈代谢和动态平衡至关重要 功能。此外，它们的调制可能会导致 细胞以逃避免疫识别。目前的建议是 关注三种这样的蛋白质：衰变加速因子 (DAF)、乙酰胆碱酯酶和Thy-1。这项提议非常有说服力 跨学科--无论从概念上还是从技术上 观点--并利用化学、细胞生物学、生化、 分子生物学和免疫学方法。这个 对锚杆结构的广泛研究 乙酰胆碱酯酶利用人红细胞；研究 THY-1专注于一个五人小鼠淋巴瘤突变体家族 合成Thy-1但不能在细胞表面表达， 显然是由于无法合成其锚；这些研究 与对照组的体液、组织和培养细胞有关 个人和患有阵发性夜间行为的个人 血红蛋白尿(PNH)。在这种疾病中，细胞表面DAF(和 乙酰胆碱酯酶)是严重缺乏的，尽管是前体 合成了多种DAF。PNH中的潜在因素可能， 因此，可能与Thy-1阴性突变体相关。这个 拟议研究的统一主题是结构， 糖磷脂锚定的生物合成与功能(S)。

Plasma membrane proteins anchored via a glycophospholipid are of critical importance for a number of metabolic and homeostatic functions. Moreover, their modulation may result in the ability of cells to escape immune recognition. The present proposal is concerned with three such proteins: decay accelerating factor (DAF), acetylcholinesterase, and Thy-1. The proposal is highly inter-disciplinary--both from a conceptual and from a technical point of view--and exploits chemical, cell biological, biochemical, molecular biological and immunological approaches. The extensive investigation of the structure of the anchor of acetylcholinesterase makes use of human red cells; the studies of Thy-1 focus on a family of five mouse lymphoma mutants which synthesize Thy-1 but fail to express it on the cell surface, apparently due to an inability to synthesize its anchor; the studies of DAF concern fluids, tissues and cultured cells of control individuals and of individuals suffering from paroxysmal nocturnal hemoglobinuria (PNH). In this disease, cell surface DAF (and acetylcholinesterase) are grossly deficient, although precursor species of DAF are synthesized. The underlying in PNH may, therefore, be related to those of the Thy-1 negative mutants. The unifying theme of the proposed research is the structure, biosynthesis and function(s) of glycophospholipid anchors.