| First Author | Watanabe Y | Year | 2013 |
| Journal | J Allergy Clin Immunol | Volume | 132 |
| Issue | 3 | Pages | 648-655.e1 |
| PubMed ID | 23684068 | Mgi Jnum | J:319008 |
| Mgi Id | MGI:6862314 | Doi | 10.1016/j.jaci.2013.03.046 |
| Citation | Watanabe Y, et al. (2013) T-cell receptor ligation causes Wiskott-Aldrich syndrome protein degradation and F-actin assembly downregulation. J Allergy Clin Immunol 132(3):648-655.e1 |
| abstractText | BACKGROUND: Wiskott-Aldrich syndrome protein (WASP) links T-cell receptor (TCR) signaling to the actin cytoskeleton. WASP is normally protected from degradation by the Ca(++)-dependent protease calpain and by the proteasome because of its interaction with the WASP-interacting protein. OBJECTIVE: We investigated whether WASP is degraded after TCR ligation and whether its degradation downregulates F-actin assembly caused by TCR ligation. METHODS: Primary T cells, Jurkat T cells, and transfected 293T cells were used in immunoprecipitation experiments. Intracellular F-actin content was measured in splenic T cells from wild-type, WASP-deficient, and c-Casitas B-lineage lymphoma (Cbl)-b-deficient mice by using flow cytometry. Calpeptin and MG-132 were used to inhibit calpain and the proteasome, respectively. RESULTS: A fraction of WASP in T cells was degraded by calpain and by the ubiquitin-proteasome pathway after TCR ligation. The Cbl-b and c-Cbl E3 ubiquitin ligases associated with WASP after TCR signaling and caused its ubiquitination. Inhibition of calpain and lack of Cbl-b resulted in a significantly more sustained increase in F-actin content after TCR ligation in wild-type T cells but not in WASP-deficient T cells. CONCLUSION: TCR ligation causes WASP to be degraded by calpain and to be ubiquitinated by Cbl family E3 ligases, which targets it for destruction by the proteasome. WASP degradation might provide a mechanism for regulating WASP-dependent TCR-driven assembly of F-actin. |
