title: Cutting edge: rho activation and actin polarization are dependent on plexin-A1 in dendritic cells.
abstract: 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.
authors.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Eun
authors.forename: Brian P
authors.initials: BP
authors.lastname: O'Connor
authors.forename: Athena W
authors.initials: AW
authors.lastname: Wong
authors.forename: Hendrick W
authors.initials: HW
authors.lastname: van Deventer
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Taxman
authors.forename: William
authors.initials: W
authors.lastname: Reed
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Janice S
authors.initials: JS
authors.lastname: Blum
authors.forename: Karen P
authors.initials: KP
authors.lastname: McKinnon
authors.forename: Jenny P-Y
authors.initials: JP
authors.lastname: Ting
mesh_terms: 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*
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D009419:Nerve Tissue Proteins; C492114:Plxna1 protein, mouse; D011956:Receptors, Cell Surface; D020741:rho GTP-Binding Proteins