Rho GTPases link cytoskeletal rearrangements and activation processes induced via the tetraspanin CD82 in T lymphocytes.

摘要: Activation of T lymphocytes requires the engagement T-cell receptor and costimulation molecules through cell-to-cell contacts. The tetraspanin CD82 has previously been shown to act as a cytoskeleton-dependent molecule. We show here that leads tyrosine phosphorylation association both Rho GTPases guanosine exchange factor Vav1 adapter protein SLP76, suggesting participate in signaling. Indeed, broad inactivation all GTPases, or specific blockade RhoA, Rac1 Cdc42, inhibited morphological changes linked but failed modulate inducible with actin network. GTPase inactivation, well depolymerization, reduced ability phosphorylate Vav SLP76 potentiate two early TcR signaling intermediates: kinases ZAP70 membrane LAT. Taken together, this suggests an amplification loop, via phosphorylations Rho-GTPases activation, is initiated by cytoskeleton, which permits cytoskeletal rearrangements costimulatory activity. Moreover, involvement formation immunological synapse strongly suggested its accumulation at site engagement. This novel link between cascade could explain why tetraspanins, are known form heterocomplexes, involved cell adhesion, growth metastasis.