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Membrane cholesterol modulates the hyaluronanbinding ability of CD44 in T lymphocytes and controls rolling under shear flow.
- Source :
-
Journal of Cell Science . Aug2013, Vol. 126 Issue 15, p3284-3294. 11p. - Publication Year :
- 2013
-
Abstract
- The adhesion of circulating lymphocytes to the surface of vascular endothelial cells is important for their recruitment from blood to secondary lymphoid organs and to inflammatory sites. CD44 is a key adhesion molecule for this interaction and its ligand-binding ability is tightly regulated. Here we show that the hyaluronan-binding ability of CD44 in T cells is upregulated by the depletion of membrane cholesterol with methyl-β-cyclodextrin (MβCD), which disintegrates lipid rafts, i.e. cholesterol- and sphingolipid-enriched membrane microdomains. Increasing concentrations of MβCD led to a dose-dependent decrease in cellular cholesterol content and to upregulation of hyaluronan binding. Additionally, a cholesterol-binding agent filipin also increased hyaluronan binding. Cholesterol depletion caused CD44 to be dispersed from cholesterol-enriched membrane microdomains. Cholesterol depletion also increased the number of cells undergoing rolling adhesion under physiological flow conditions. Our results suggest that the ligand-binding ability of CD44 is governed by its cholesterol-dependent allocation to membrane microdomains at the cell surface. These findings provide novel insight into the regulation of T cell adhesion under blood flow. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219533
- Volume :
- 126
- Issue :
- 15
- Database :
- Academic Search Index
- Journal :
- Journal of Cell Science
- Publication Type :
- Academic Journal
- Accession number :
- 89772780
- Full Text :
- https://doi.org/10.1242/jcs.120014