Wortmannin inhibits transcytosis of dimeric IgA by the polymeric immunoglobulin receptor.
Phosphatidyl inositol 3-kinase (PI3K) plays an essential role in numerous signaling events, and increasingly has been implicated in regulation of certain membrane traffic events. The polymeric immunoglobulin receptor (pIgR) transcytoses dimeric IgA (dIgA) across epithelial cells and into external secretions, where the dIgA forms the first specific immunological defense against infection. We show here that wortmannin, a highly specific inhibitor of PI3K, inhibits transcytosis of dIgA by the pIgR. Instead, the dIgA is recycled back to the basolateral surface of the epithelial cell. PI3K therefore plays an essential role in regulating the transcytosis of dIgA, a key step in the mucosal immune response.
Department of Anatomy, University of California, San Francisco 94143-0452, USA.
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Cardone
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Mostov
D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007070:Immunoglobulin A / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors*; D019056:Receptors, Polymeric Immunoglobulin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014162:Transfection / Q000235:genetics; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D007070:Immunoglobulin A; D019056:Receptors, Polymeric Immunoglobulin; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D000077191:Wortmannin