GPI ANCHORED PROTEIN DEFICIENCIES IN CELLS FROM PSORIATIC SKIN

银屑病皮肤细胞中 GPI 锚定蛋白缺陷

• 批准号: 6235778
• 负责人: Mark Lehrman
• 金额: $ 5.04万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-10 至 1998-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6235778
• 关键词: CD antigens; biopsy; fibroblasts; gene expression; glycolipids; glycosylphosphatidylinositols; human tissue; keratinocyte; lipid biosynthesis; lipid metabolism; membrane lipids; peptides; phosphatidylinositols; polysaccharides; protein biosynthesis; protein degradation; protein metabolism; psoriasis; tissue /cell culture

Abroad spectrum of eukaryotic proteins are attached to cell surfaces by glycosylphosphatidylinositol (GPI) anchors. Such proteins include neuronal cell adhesion molecule, decay accelerating factor, scrapie prion protein, folate receptor, Thy-1 antigen, and the trypanosoma variant surface glycoprotein. The central features of GPI anchors are: (I) a residue of phosphatidylinositol, which is embedded in the plasma membrane; and (ii) a linear glycan stalk (1 glucosamine residue followed by 3 mannose residues, with a residue of ethanolamine-P linked to the 3rd mannose) with a glycosidic linkage attaching the glucosamine residue to the inositol residue of the phosphatidylinositol. The carboxy-terminal ends of protein molecules are attached to preassembled GPI anchors through the amine group of the ethanolamine-P. Psoriasis is a skin disease which affects many individuals, but its cause is unknown. Recently, histochemical analyses have suggested that GPI anchored proteins are highly deficient in psoriatic skin. This could be caused by (a) defective synthesis of preassembled anchors; (b) failure to attach anchors to proteins; ~ enzymatic cleavage of the anchors by phospholipases; and/or (d) proteolytic degradation of GPI anchored proteins. Methods for studying all of these possibilities have been described in the literature in detail, and are available in the P.I.~s laboratory. Experiments in this proposal will determine directly whether biosynthesis or catabolism of GPI anchored proteins is defective in cells derived from patients with psoriasis skin. The approach is to apply proven methods for GPI-anchor analysis to primary cultures of psoriatic fibroblasts and keratinocytes. In addition, a novel approach based upon recent research in the P.I.~s laboratory involving the use of synthetic GPI analogues will also be used to address this question.

真核生物蛋白的光谱广泛存在于细胞上