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Lipid rafts mediate biosynthetic transport to the T lymphocyte uropod subdomain and are necessary for uropod integrity and function
|Authors:||Millán, Jaime ; Montoya, María C.; Sancho, David; Sánchez-Madrid, Francisco; Alonso, Miguel A.|
|Publisher:||American Society of Hematology|
|Citation:||Blood 99: 978-984 (2002)|
|Abstract:||Polarized migrating T cells possess 2 poles, the uropod protrusion at the rear and the leading edge at the front, with specific protein composition and function. The influenza virus hemagglutinin (HA) is a prototypical molecule that uses lipid rafts for biosynthetic transport to the apical surface in polarized epithelial Madin-Darby canine kidney (MDCK) cells. In this study, HA was used as a tool to investigate the role of lipid rafts in vectorial protein traffic in polarized T lymphocytes. Results show that newly synthesizedHAbecomes selectively targeted to the uropod subdomain in polarized T lymphoblasts. HA incorporates into rafts soon after biosynthesis, suggesting that delivery of HA to the uropod occurs through a pathway of transport reminiscent of that used for its specific targeting to the apical surface. HA and the adhesion molecules, intercellular adhesion molecule 3 (ICAM-3), CD44, and CD43, 3 endogenous uropod markers, were detected in surface rafts of T lymphoblasts. Cholesterol, a major component of lipid rafts, was predominantly located in the uropod. Disruption of lipid raft integrity by cholesterol sequestration produced unclustering of ICAM-3 and the loss of uropodia and severely impaired processes that require a polarized phenotype such as intercellular aggregation and cell migration. Collectively, these results indicate that lipid rafts constitute a route for selective targeting of proteins to the uropod and that the rafts are essential for the generation, maintenance, and functionality of T-cell anteroposterior polarity.|
|Description:||7 páginas, 6 figuras.|
|Publisher version (URL):||http://dx.doi.org/10.1182/blood.V99.3.978|
|Appears in Collections:||(CBM) Artículos|
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