Cytoskeletal Regulation of CD44 Membrane Organization and Interactions with E-selectin

Abstract

Background: CD44 on neutrophils is a ligand for E-selectin on endothelial cells. Results: CD44 forms actin-dependent clusters by binding to ezrin/radixin/moesin (ERM) proteins and ankyrin. Conclusion: Cytoskeletal interactions regulate CD44 clustering, mobility, and function. Significance: CD44 organizes at nanometer scale on cell surfaces.

TNF-Stimulated Gene-6 Is a Key Regulator in Switching Stemness and Biological Properties of Mesenchymal Stem Cells

“…TSG‐6 is a potent modulator of HA binding to CD44 on lymphoid cell lines , which likely regulates leukocyte migration to the sites of inflammation. Interestingly, a recent study has demonstrated that the cell surface distribution of CD44 can restrict the movement of other receptors and influence the organization of the actin cytoskeleton . Our flow cytometry analyses revealed a reduction in the expression of CD44 on the surface of TSG‐6 −/− ‐MSCs compared with WT cells.…”

Quantitative Characterization of E-selectin Interaction with Native CD44 and P-selectin Glycoprotein Ligand-1 (PSGL-1) Using a Real Time Immunoprecipitation-based Binding Assay

“…Using the assay outlined here, it would be difficult, however, to address the effect of ligand oligomerization on binding to E-selectin. The oligomerization state of the captured molecules is unknown and is likely heterogeneous (52), but also the state of the ligands on the cell membrane is different from that in solution because at least in some cases this oligomerization is regulated by the cell cytoskeleton. To further understand the contribution of ligand clustering to binding kinetics using an SPR approach, future experiments may be developed to use live cells where manipulation of the ligands in the cell membrane could be tested.…”

“…This clustering is likely mediated via interactions with the cytoskeleton either directly through adaptor proteins, such as ezrin/radixin/moesin and ankyrin, or indirectly through proteins enriched within lipid rafts (51,52). Interestingly, a recent study suggested that the clustering mediated by ankyrin binding to the cytoplasmic domain of CD44 enhances its binding to E-selectin under flow (52). Using the assay outlined here, it would be difficult, however, to address the effect of ligand oligomerization on binding to E-selectin.…”

Juxtamembrane contribution to transmembrane signaling

“…In some cases, the JM region, instead of the transmembrane helix, appears to drive the association . In addition, the intracellular JM region in many adhesion receptors is enriched with basic residues and involved in the efficient surface expression of the receptor or the association with intracellular signaling or cytoskeletal proteins . Nevertheless, how the JM region propagates or modulates the outside‐in signaling of adhesion receptors remains to be delineated.…”