| First Author | Massaad MJ | Year | 2014 |
| Journal | Mol Cell Biol | Volume | 34 |
| Issue | 23 | Pages | 4343-54 |
| PubMed ID | 25246631 | Mgi Jnum | J:224328 |
| Mgi Id | MGI:5662028 | Doi | 10.1128/MCB.00533-14 |
| Citation | Massaad MJ, et al. (2014) Binding of WIP to actin is essential for T cell actin cytoskeleton integrity and tissue homing. Mol Cell Biol 34(23):4343-54 |
| abstractText | The Wiskott-Aldrich syndrome protein (WASp) is important for actin polymerization in T cells and for their migration. WASp-interacting protein (WIP) binds to and stabilizes WASp and also interacts with actin. Cytoskeletal and functional defects are more severe in WIP(-/-) T cells, which lack WASp, than in WASp(-/-) T cells, suggesting that WIP interaction with actin may be important for T cell cytoskeletal integrity and function. We constructed mice that lack the actin-binding domain of WIP (WIPDeltaABD mice). WIPDeltaABD associated normally with WASp but not F-actin. T cells from WIPDeltaABD mice had normal WASp levels but decreased cellular F-actin content, a disorganized actin cytoskeleton, impaired chemotaxis, and defective homing to lymph nodes. WIPDeltaABD mice exhibited a T cell intrinsic defect in contact hypersensitivity and impaired responses to cutaneous challenge with protein antigen. Adoptively transferred antigen-specific CD4(+) T cells from WIPDeltaABD mice had decreased homing to antigen-challenged skin of wild-type recipients. These findings show that WIP binding to actin, independently of its binding to WASp, is critical for the integrity of the actin cytoskeleton in T cells and for their migration into tissues. Disruption of WIP binding to actin could be of therapeutic value in T cell-driven inflammatory diseases. |
