Pivotal roles of both Wiskott-Aldrich syndrome protein (WASP) and N-WASP in the activation and attenuation of the B cell receptor (P1093) (42.1)
| Autor: | Chaohong Liu, Shruti Sharma, Heather Miller, Arpita Upadhyaya, Carin Dahlberg, Lisa Westerberg, Scott Snapper, Wenxia Song |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 188:42.1-42.1 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.188.supp.42.1 |
| Popis: | Lymphocytes express both Wiskott-Aldrich syndrome protein (WASP) and N-WASP. WASP deficiency, the cause of WAS, generates more severe defects in T-cells than B cells, suggesting a strong compensatory role of N-WASP in B cells. Using knockout mouse models, this study shows that WASP knockout (WKO) reduces B cell spreading, B cell receptor (BCR) aggregation, tyrosine phosphorylation, Btk phosphorylation and F-actin accumulation at the B cell surface induced by membrane-associated antigen, and WASP/N-WASP double knockout nearly abolished these activities. However, in B cells with N-WASP conditional knockout (cNKO), B cell spreading and F-actin accumulation are enhanced, while the merge of BCR aggregates and attenuation of tyrosine and Btk phosphorylation are inhibited. Additionally, cNKO has a much stronger inhibitory effect on BCR endocytosis than WKO. In contrast to Btk-dependent activation of WASP, N-WASP phosphorylation is upregulated by Btk-deficiency but downregulated by SHIP KO. Furthermore, the phosphorylation of WASP and N-WASP is inversely regulated by each other. These results reveal that the combined function of WASP and N-WASP is required for the optimal activation of the BCR and its signaling attenuation, but these two proteins function distinctively: WASP and N-WASP play dominant roles in the initiation and attenuation of BCR activation respectively. Thus, the integrated action of WASP and N-WASP provide a critical regulatory mechanism for BCR activation. |
| Databáze: | OpenAIRE |
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