Involvement of CD44 in cytoskeleton rearrangement and raft reorganization in T cells.
T cell activation is accompanied by actin-mediated receptor clustering and reorganization of lipid rafts. It has been suggested that costimulatory molecules might be involved in these processes. We here provide evidence that engagement of the adhesion molecule CD44 initiates cytoskeletal rearrangement and membrane reorganization in T cells. Cross-linking of CD44 on a T helper line was accompanied by adhesion, spreading and actin bundle formation. These processes were energy dependent and required an intact actin and microtubule system. They involved the small GTPase Rac as evidenced by the absence of spreading in cells overexpressing a dominant negative form of Rac. The CD44 initiated reorganization of the cytoskeleton was associated with the recruitment of CD44 and the associated tyrosine phosphokinases p56(lck) and p59(fyn) into glycolipid enriched membrane microdomains (GEM). We interpret the data in the sense that CD44 functions as a costimulatory molecule in T cell activation by inducing actin cytoskeletal rearrangements and membrane protein and lipid reorganization including its association with GEMs. Due to the association of CD44 with lck and fyn this colocalization with the TCR allows an abundant provision of these kinases, which are essential to initiate the TCR signaling cascade.
Föger
N
N
Department of Tumor Progression and Immune Defense, German Cancer Research Center, Heidelberg, Germany.
Marhaba
R
R
Zöller
M
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D003432:Cross-Linking Reagents; D003599:Cytoskeleton / Q000502:physiology*; D018960:Hyaluronan Receptors / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D021382:Protein Sorting Signals; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism* / Q000502:physiology
D003432:Cross-Linking Reagents; D018960:Hyaluronan Receptors; D021382:Protein Sorting Signals