Redistribution of specialized molecules in migrating cells develops asymmetry between two opposite cell poles, the leading edge and the uropod. We show that acquisition of a motile phenotype in T lymphocytes results in the asymmetric redistribution of ganglioside GM3-and GM1-enriched raft domains to the leading edge and to the uropod, respectively. This segregation to each cell pole parallels the specific redistribution of membrane proteins associated to each raft subfraction. Our data suggest that raft partitioning is a major determinant for protein redistribution in polarized T cells, as ectopic expression of raft-associated proteins results in their asymmetric redistribution, whereas non-raft-partitioned mutants of these proteins are distributed homogeneously in the polarized cell membrane. Both acquisition of a migratory phenotype and SDF-1␣-induced chemotaxis are cholesterol depletion-sensitive. Finally, GM3 and GM1 raft redistribution requires an intact actin cytoskeleton, but is insensitive to microtubule disruption. We propose that membrane protein segregation not only between raft and nonraft domains but also between distinct raft subdomains may be an organizational principle that mediates redistribution of specialized molecules needed for T cell migration. Cell movement across a two-dimensional substrate requires a dynamic interplay between attachment at the cell front and detachment at the rear cell edge, combined with a traction machinery that pulls the net cell body forward. As adhesion and detachment occur at opposite cell edges, the moving cell must acquire and maintain spatial and functional asymmetry, a process called polarization (1, 2). This asymmetry develops between two opposite cell edges-the leading edge, which protrudes, and the rear (termed uropod in lymphocytes), which retracts.Because of the specialized functions of these compartments, each pole in migrating cells is enriched in specific receptors and signaling molecules but lacks others. In fibroblast-like cells and lymphocytes, the leading edge contains chemokine receptors, several glycosylphosphatidylinositol-linked proteins, such as the urokinase plasminogen activator receptor (uPAR), as well as the machinery that senses the environment and induces localized actin polymerization (1). Whereas the rear edge in fibroblasts appears to be a passive tail, the lymphocyte uropod is a specialized pseudopod-like projection with important functions, including motility and recruitment of bystander cells. Several intercellular adhesion molecules (ICAMs) concentrate at the uropod, including ICAM-1, -2 and -3, CD43, CD44, as well as the actin-binding proteins of the ezrin-radixinmoesin family. In accordance with its importance in lymphocyte migration, crosslinking of molecules located in the uropod is sufficient to trigger neutrophil polarization and motility (3).To understand polarization and chemotaxis processes, the molecular mechanisms involved in the generation and maintenance of the asymmetric distribution of cell-surface components must be...
HIV-1 infection triggers lateral membrane diffusion following interaction of the viral envelope with cell surface receptors. We show that these membrane changes are necessary for infection, as initial gp120-CD4 engagement leads to redistribution and clustering of membrane microdomains, enabling subsequent interaction of this complex with HIV-1 co-receptors. Disruption of cell membrane rafts by cholesterol depletion before viral exposure inhibits entry by both X4 and R5 strains of HIV-1, although viral replication in infected cells is unaffected by this treatment. This inhibitory effect is fully reversed by cholesterol replenishment of the cell membrane. These results indicate a general mechanism for HIV-1 envelope glycoprotein-mediated fusion by reorganization of membrane microdomains in the target cell, and offer new strategies for preventing HIV-1 infection.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.