Cutting edge: rho activation and actin polarization are dependent on plexin-A1 in dendritic cells.
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.
Eun
So-Young
SY
Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
O'Connor
Brian P
BP
Wong
Athena W
AW
van Deventer
Hendrick W
HW
Taxman
Debra J
DJ
Reed
William
W
Li
Ping
P
Blum
Janice S
JS
McKinnon
Karen P
KP
Ting
Jenny P-Y
JP
D051339:Actin Depolymerizing Factors / Q000494:pharmacology; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D005434:Flow Cytometry; D015870:Gene Expression; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D020741:rho GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism*
D051339:Actin Depolymerizing Factors; D000199:Actins; D009419:Nerve Tissue Proteins; C492114:Plxna1 protein, mouse; D011956:Receptors, Cell Surface; D020741:rho GTP-Binding Proteins