INHIBITION OF RETROMER BY HVS TIP

HVS Tip 对 RETROMER 的抑制

• 批准号: 7715518
• 负责人: Jae U Jung
• 金额: $ 3.24万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-05 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715518
• 关键词: Acquired Immunodeficiency Syndrome; Complex; Computer Retrieval of Information on Scientific Projects Database; Early Endosome; Endosomes; Funding; Glutamic Acid; Grant; Human; Hydrolase; Institution; Lysosomes; Measures; Proteins; Pyrococcus kodakaraensis TIP protein; Reporting; Research; Research Personnel; Resources; Saimiriine Herpesvirus 2; Source; Swelling; T-Lymphocyte; United States National Institutes of Health; Viral Proteins; human IGF2R protein; retrograde transport; trans-Golgi Network

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Transformation of human T lymphocytes by Herpesvirus saimiri (HVS) is dependent on expression of the viral protein Tip and its manipulation of cellular proteins. Here, we report that the conserved glutamic acid-rich domain of Tip interacted with the retromer subunit Vps35. The retromer complex is required for efficient retrograde transport of the cation-independent mannose-6-phosphate receptor (CI-MPR) from the endosome to the trans-Golgi network. Expression of Tip not only caused redistribution of Vps35 from the early endosome to the lysosome and swelling of the lysosomal compartments, but also drastically inhibited retromer activity as measured by decreased CI-MPR levels and lower activities of cellular lysosomal hydrolases. AIDS related.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 疱疹病毒 saimiri (HVS) 对人类 T 淋巴细胞的转化依赖于病毒蛋白 Tip 的表达及其对细胞蛋白的操作。在这里，我们报道了 Tip 保守的富含谷氨酸的结构域与逆转录体亚基 Vps35 相互作用。逆转录体复合物对于将不依赖于阳离子的甘露糖-6-磷酸受体（CI-MPR）从内体有效逆行转运至跨高尔基体网络而言是必需的。 Tip 的表达不仅引起 Vps35 从早期内体到溶酶体的重新分配以及溶酶体区室的肿胀，而且通过 CI-MPR 水平降低和细胞溶酶体水解酶活性降低来测量，还显着抑制了逆转录酶活性。艾滋病相关。