M. Villalba et al., Vav1/Rac-dependent actin cytoskeleton reorganization is required for lipidraft clustering in T cells, J CELL BIOL, 155(3), 2001, pp. 331-338
Formation of the immunological synapse (IS) in T cells involves large scale
molecular movements that are mediated, at least in part, by reorganization
of the actin cytoskeleton. Various signaling proteins accumulate at the IS
and are localized in specialized membrane microdomains, known as lipid raf
ts. We have shown previously that lipid rafts cluster and localize at the I
S in antigen-stimulated T cells. Here, we provide evidence that lipid raft
polarization to the IS depends on an intracellular pathway that involves Va
v1, Rac, and actin cytoskeleton reorganization. hus, lipid rafts did not tr
anslocate to the IS in Vav1-deficient (Vav1(-/-)) T cells upon antigen stim
ulation. Similarly, T cell receptor transgenic Jurkat T cells also failed t
o translocate lipid rafts to the IS when transfected with dominant negative
Vav1 mutants. Raft polarization induced by membrane-bound cholera toxin cr
oss-linking was also abolished in Jurkat T cells expressing dominant negati
ve Vav1 or Rac mutants and in cells treated with inhibitors of actin polyme
rization. However, Vav overexpression that induced F-actin polymerization f
ailed to induce lipid rafts clustering. Therefore, Vav is necessary, but no
t sufficient, to regulate lipid rafts clustering and polarization at the IS
, suggesting that additional signals are required.