GLYCOLIPID PROTEIN ANCHORS IN PNH AND THY-1 MUTANTS

通过糖磷脂锚定的质膜蛋白是 对许多代谢和体内平衡至关重要 功能协调发展的 此外，它们的调节可能导致以下能力： 细胞逃避免疫识别。 现时的建议是 与三种这样的蛋白质有关：衰变加速因子 (DAF)、乙酰胆碱酯酶和Thy-1。 该提案高度 跨学科--无论是从概念上还是从技术上， 并利用化学，细胞生物学，生物化学， 分子生物学和免疫学方法。 的 广泛调查的锚的结构， 乙酰胆碱酯酶利用人体红细胞; Thy-1关注一个由五个小鼠淋巴瘤突变体组成的家族， 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;研究 与对照组的体液、组织和培养细胞无关的 个人和个人患有阵发性夜间 血红蛋白尿（PNH）。 在这种疾病中， 乙酰胆碱酯酶）严重缺乏，虽然前体 合成了各种各样的化合物。 PNH中的基础可能， 因此，与Thy-1阴性突变体相关。 的 拟议研究的统一主题是结构， 糖磷脂锚的生物合成和功能。

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.