DIRECTIONAL TRANSPORT OF MULV GLYCOPROTEINS

MULV糖蛋白的定向运输

• 批准号: 3164988
• 负责人: RICHARD W COMPANS
• 金额: $ 12.75万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-06-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3164988
• 关键词: Retroviridae; Retroviridae disease; basolateral membrane; biological signal transduction; epithelium; flow cytometry; gene expression; genetic manipulation; genetic mapping; genetic recombination; genetic translation; glycoproteins; immunofluorescence technique; intracellular transport; laboratory mouse; membrane proteins; molecular oncology; monoclonal antibody; murine leukemia virus; mutant; neoplasm /cancer genetics; nucleocapsid; peptides; protein biosynthesis; protein signal sequence; protein structure; secretory protein; temperature sensitive mutant; tissue /cell culture; transfection; transport proteins; vaccinia virus; viral leukemogenesis; virus characteristic; virus envelope; virus genetics; virus infection mechanism; virus protein; virus replication; viruslike particle

Our objective is to define the molecular basis by which membrane glycoproteins are directionally transported to specific cellular locations. These investigations will be carried out using viral glycoproteins which are transported to different plasma membrane domains on surfaces of polarized epithelial cells. To identify sorting signals responsible for the directional transport of glycoproteins, we will analyze the effects of specific modifications and sequence substitutions on determining the cellular location of the resulting molecules. These studies will be carried out with viral glycoproteins which exhibit distinct orientations and transmembrane topology: the gp70/p15E glycoprotein of murine leukemia viruses, a bitopic membrane glycoprotein with a cleaved signal sequence that is anchored by hydrophobic residues near the C-terminus of the molecule, and the gPr-gag glycoprotein which is likely to be anchored to membranes in the opposite orientation. In order to characterize the intracellular transport pathway of MuLV glycoproteins, we will use specific antisera to identify transport vesicles involved in movement of glycoproteins from the Golgi complex to the plasma membrane. We will determine whether the two MuLV-encoded glycoproteins gp70/p15E and gPr-gag are present in the same population of transport vesicles and whether they are associated with one another on the plasma membrane. To further define the viral components which are involved in determining the maturation site of retroviruses in epithelial cells, we will investigate the site of virus assembly and release in cells which produce viral cores in the absence of viral glycoproteins, and determine the effects of supplementing these cells with viral glycoproteins directed to either the apical or basolateral membranes. In addition to providing a better understanding of basic cellular processes, the proposed studies should contribute to our knowledge concerning the pathogenesis of viral infections by elucidating the mechanisms by which viral components are targeted to particular locations.

我们的目标是确定膜的分子基础 糖蛋白被定向运输到特定的细胞 地点 这些调查将使用病毒 糖蛋白被转运到不同的质膜结构域， 极化上皮细胞表面。 识别分选信号 负责糖蛋白的定向运输，我们将分析 特异性修饰和序列置换对 确定所得分子的细胞位置。 这些 将对病毒糖蛋白进行研究， 方向和跨膜拓扑结构：gp 70/p15 E糖蛋白的 小鼠白血病病毒，一种双位点膜糖蛋白， 由疏水残基锚定的信号序列， 分子的C-末端，以及可能与其结合的gPr-gag糖蛋白。 以相反的方向锚定到膜上。 为了 描述了MuLV糖蛋白的细胞内转运途径，我们 将使用特异性抗血清来鉴定参与 糖蛋白从高尔基复合体向质膜的移动。 我们将确定两种MuLV编码的糖蛋白gp 70/p15 E和p15 E是否与MuLV的表达有关。 gPr-gag存在于相同的运输囊泡群体中， 它们是否在质膜上相互结合。 到 进一步定义参与确定病毒的病毒成分， 逆转录病毒在上皮细胞中的成熟位点，我们将研究 在产生病毒核心的细胞中病毒装配和释放的位点 在没有病毒糖蛋白的情况下，并确定 用病毒糖蛋白补充这些细胞， 顶膜或基底膜。 除了提供更好的 了解基本的细胞过程，拟议的研究应该 有助于我们了解病毒感染的发病机制 通过阐明病毒成分靶向 特定地点。