Rho GTPases link cytoskeletal rearrangements and activation processes induced via the tetraspanin CD82 in T lymphocytes
| Autor: | Alix Delaguillaumie, Cécile Lagaudrière-Gesbert, Michel R. Popoff, Hélène Conjeaud |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
rho GTP-Binding Proteins
RHOA T-Lymphocytes Cell Cycle Proteins RAC1 CDC42 GTPase Kangai-1 Protein Lymphocyte Activation Cell Membrane Structures Jurkat Cells chemistry.chemical_compound Tetraspanin Antigens CD Proto-Oncogene Proteins Humans Phosphorylation Proto-Oncogene Proteins c-vav cdc42 GTP-Binding Protein Cytoskeleton Adaptor Proteins Signal Transducing Membrane Glycoproteins biology T-cell receptor Tyrosine phosphorylation Cell Biology Phosphoproteins rac GTP-Binding Proteins Cell biology chemistry Receptor-CD3 Complex Antigen T-Cell biology.protein Tyrosine Signal Transduction |
| Zdroj: | Journal of Cell Science. 115:433-443 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.115.2.433 |
| Popis: | Activation of T lymphocytes requires the engagement of the T-cell receptor and costimulation molecules through cell-to-cell contacts. The tetraspanin CD82 has previously been shown to act as a cytoskeleton-dependent costimulation molecule. We show here that CD82 engagement leads to the tyrosine phosphorylation and association of both the Rho GTPases guanosine exchange factor Vav1 and adapter protein SLP76, suggesting that Rho GTPases participate in CD82 signaling. Indeed, broad inactivation of all Rho GTPases, or a specific blockade of RhoA, Rac1 or Cdc42, inhibited the morphological changes linked to CD82 engagement but failed to modulate the inducible association of CD82 with the actin network. Rho GTPase inactivation, as well as actin depolymerization, reduced the ability of CD82 to phosphorylate Vav and SLP76 and to potentiate the phosphorylation of two early TcR signaling intermediates: the tyrosine kinases ZAP70 and membrane adapter LAT. Taken together, this suggests that an amplification loop, via early Vav and SLP76 phosphorylations and Rho-GTPases activation, is initiated by CD82 association with the cytoskeleton, which permits cytoskeletal rearrangements and costimulatory activity. Moreover, the involvement of CD82 in the formation of the immunological synapse is strongly suggested by its accumulation at the site of TcR engagement. This novel link between a tetraspanin and the Rho GTPase cascade could explain why tetraspanins, which are known to form heterocomplexes, are involved in cell activation, adhesion, growth and metastasis. |
| Databáze: | OpenAIRE |
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