INHIBITION OF RETROMER BY HVS TIP

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 疱疹病毒塞米里病毒对人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调控。在这里，我们报告了TiP的保守的谷氨酸富集区与逆转录聚合子亚单位VPS35相互作用。逆转录复合体是阳离子非依赖性甘露糖-6-磷酸受体(CI-MPR)从内体到反式高尔基体网络的有效逆行运输所必需的。Tip的表达不仅导致VPS35从早期的内体重新分布到溶酶体和溶酶体室的肿胀，而且还显著抑制了逆转聚体的活性，表现为CI-MPR水平的降低和细胞溶酶体水解酶的活性降低。与艾滋病有关。

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.