| First Author | Ocana-Morgner C | Year | 2009 |
| Journal | Blood | Volume | 113 |
| Issue | 7 | Pages | 1474-82 |
| PubMed ID | 18802007 | Mgi Jnum | J:145454 |
| Mgi Id | MGI:3834775 | Doi | 10.1182/blood-2008-04-152587 |
| Citation | Ocana-Morgner C, et al. (2009) SWAP-70 regulates RhoA/RhoB-dependent MHCII surface localization in dendritic cells. Blood 113(7):1474-82 |
| abstractText | Stimulated dendritic cells (DCs) mature and migrate to lymphoid organs to prime naive T cells. DC maturation augments antigen-presentation capacity of DCs by increasing peptide loading, half-life, and cell surface localization of MHC molecules. Activated SWAP-70(-/-) DCs fail to properly localize MHCII molecules in the plasma membrane, are strongly impaired in T-cell activation, and are altered in F-actin rearrangement. MHCII synthesis, invariant chain removal, and MHCII internalization, however, are unaffected. MHCII surface localization is known to require RhoGTPases. Surprisingly, SWAP70, hitherto known to bind F-actin and Rac, also binds RhoA-GTP. In SWAP-70(-/-) DCs, RhoA and RhoB are stimulus-independent and constitutively active. Surface localization of MHCII molecules and T-cell activation can be restored by blocking RhoA and RhoB before but not during DC activation. Thus, contrasting positive regulation of Rac, SWAP-70 negatively regulates RhoA and-indirectly-RhoB, preventing premature RhoA/RhoB activation. Through RhoA/RhoB regulation, SWAP-70 defines a new pathway to control surface localization of MHCII, a critical element in DC-dependent immune responses. |
