This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
Showing the most recent 10 out of 365 publications