Abstract
Lipid rafts are membrane microdomains that function as platforms for signal transduction and membrane trafficking. Tyrosine kinase interacting protein (Tip) of T lymphotropic Herpesvirus saimiri (HVS) is targeted to lipid rafts in T cells and downregulates TCR and CD4 surface expression. Here, we report that the membrane-proximal amphipathic helix preceding Tip's transmembrane (TM) domain mediates lipid raft localization and membrane deformation. In turn, this motif directs Tip's lysosomal trafficking and selective TCR downregulation. The amphipathic helix binds to the negatively charged lipids and induces liposome tubulation, the TM domain mediates oligomerization, and cooperation of the membrane-proximal helix with the TM domain is sufficient for localization to lipid rafts and lysosomal compartments, especially the mutivesicular bodies. These findings suggest that the membrane-proximal amphipathic helix and TM domain provide HVS Tip with the unique ability to deform the cellular membranes in lipid rafts and to downregulate TCRs potentially through MVB formation.
Highlights
Lipid rafts are membrane microdomains that take part in coordinating cell signalling functions and membrane trafficking
It has been known that Tyrosine kinase-interacting protein (Tip) may play some role in viral persistency within T cells by inhibiting the activation of the host cells upon antigenic stimulation
We found that the structural motif is essential for Tip’s localization on specialized membrane domains, lipid rafts, and selective downregulation of antigen receptors
Summary
Lipid rafts are membrane microdomains that take part in coordinating cell signalling functions and membrane trafficking. In T cells, upon antigenic stimulation, T cell receptors (TCRs) are recruited to lipid rafts, where they transmit signals via several pathways. Current evidence indicates that lipid rafts function as platforms for both the signalling and endocytosis of activated TCRs. Despite the important role of lipid rafts in signalling and membrane trafficking in T cells, the regulatory mechanisms controlling membrane trafficking to lysosomal compartments remain unclear. Several biochemically distinct compartments for membrane trafficking have been identified in other cell types including primary endocytic vesicles, early endosomes, late endosomes, and lysosomes. Difficulties in elucidating the mechanisms of membrane trafficking have been compounded in T cells, because the fate of endocytic vesicles and the dynamics of transport intermediates remain uncertain
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
