RT Journal Article
SR Electronic
T1 Cutting Edge: Rho Activation and Actin Polarization Are Dependent on Plexin-A1 in Dendritic Cells
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 4271
OP 4275
DO 10.4049/jimmunol.177.7.4271
VO 177
IS 7
A1 Eun, So-Young
A1 O’Connor, Brian P.
A1 Wong, Athena W.
A1 van Deventer, Hendrick W.
A1 Taxman, Debra J.
A1 Reed, William
A1 Li, Ping
A1 Blum, Janice S.
A1 McKinnon, Karen P.
A1 Ting, Jenny P.-Y.
YR 2006
UL http://www.jimmunol.org/content/177/7/4271.abstract
AB We recently identified expression of the semaphorin receptor, plexin-A1, in dendritic cells (DCs); however, its function in these cells remains to be elucidated. To investigate function and maximize physiological relevance, we devised a retroviral approach to ablate plexin-A1 gene expression using small hairpin RNA (shRNA) in primary bone marrow-derived DCs. We show that plexin-A1 localizes within the cytoplasm of immature DCs, becomes membrane-associated, and is enriched at the immune synapse in mature DCs. Reducing plexin-A1 expression with shRNA greatly reduced actin polarization as well as Rho activation without affecting Rac or Cdc42 activation. A Rho inhibitor, C3, also reduced actin polarization. These changes were accompanied by the near-ablation of T cell activation. We propose a mechanism of adaptive immune regulation in which plexin-A1 controls Rho activation and actin cytoskeletal rearrangements in DCs that is associated with enhanced DC-T cell interactions.