Plexin-B2 negatively regulates macrophage motility, Rac, and Cdc42 activation

• Published in: PloS one Vol. 6; no. 9; p. e24795
• Main Authors: Roney, Kelly E, O'Connor, Brian P, Wen, Haitao, Holl, Eda K, Guthrie, Elizabeth H, Davis, Beckley K, Jones, Stephen W, Jha, Sushmita, Sharek, Lisa, Garcia-Mata, Rafael, Bear, James E, Ting, Jenny P-Y
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.09.2011; Public Library of Science (PLoS)
• Subjects: Animals; Antigen presenting cells; Bacteria; Biology; Blotting, Western; Bone Marrow Cells - metabolism; cdc42 GTP-Binding Protein - metabolism; Cdc42 protein; Cell activation; Cell adhesion & migration; Cell Movement; Cell surface; Cell Transplantation - methods; Cells, Cultured; Chemotactic factors; Cytokines; Cytokines - metabolism; Cytoskeleton; Dendritic cells; Developmental biology; Drosophila; E coli; Extracellular matrix; Female; Flow Cytometry; G proteins; Guanosine triphosphate; Humans; Immune system; Immunology; Inflammation; Innate immunity; Insects; Kinases; Leukocyte Common Antigens - metabolism; Leukocyte migration; Ligands; Liver - cytology; Liver - embryology; Liver - metabolism; Macrophages; Macrophages - cytology; Macrophages - metabolism; Male; Mice; Mice, Congenic; Mice, Inbred C57BL; Mice, Knockout; Morphogenesis; Motility; Mutation; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nervous system; Phagocytosis; Prostate cancer; Protein Binding; rac1 GTP-Binding Protein - metabolism; Receptors; Signaling; Spleen - cytology; Spleen - metabolism; Wound healing; Yeast; North Carolina; United States > US; Colorado
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0024795

Plexins are cell surface receptors widely studied in the nervous system, where they mediate migration and morphogenesis though the Rho family of small GTPases. More recently, plexins have been implicated in immune processes including cell-cell interaction, immune activation, migration, and cytokine production. Plexin-B2 facilitates ligand induced cell guidance and migration in the nervous system, and induces cytoskeletal changes in overexpression assays through RhoGTPase. The function of Plexin-B2 in the immune system is unknown. This report shows that Plexin-B2 is highly expressed on cells of the innate immune system in the mouse, including macrophages, conventional dendritic cells, and plasmacytoid dendritic cells. However, Plexin-B2 does not appear to regulate the production of proinflammatory cytokines, phagocytosis of a variety of targets, or directional migration towards chemoattractants or extracellular matrix in mouse macrophages. Instead, Plxnb2(-/-) macrophages have greater cellular motility than wild type in the unstimulated state that is accompanied by more active, GTP-bound Rac and Cdc42. Additionally, Plxnb2(-/-) macrophages demonstrate faster in vitro wound closure activity. Studies have shown that a closely related family member, Plexin-B1, binds to active Rac and sequesters it from downstream signaling. The interaction of Plexin-B2 with Rac has only been previously confirmed in yeast and bacterial overexpression assays. The data presented here show that Plexin-B2 functions in mouse macrophages as a negative regulator of the GTPases Rac and Cdc42 and as a negative regulator of basal cell motility and wound healing.