Selective inhibition of transcytosis by brefeldin A in MDCK cells.
Treatment of most cells with brefeldin A (BFA) leads to the retrieval of the Golgi complex to the endoplasmic reticulum, presumably reflecting an inhibition of cytoplasmic coat protein binding to Golgi membranes. Although BFA has been thought to act only on biosynthetic organelles, we now show that this drug also reversibly blocks polymeric immunoglobulin receptor-mediated transcytosis in MDCK cells. The action of BFA on transcytosis was selective, since internalization, recycling, and intracellular degradation were unaffected. The block occurred early on the transcytotic pathway, probably before the translocation of IgA-containing vesicles from the basal to the apical cytoplasm. Although BFA caused MDCK cell endosomes to become more tubular, the organization of the Golgi and binding of the 110 kd Golgi coat protein beta-COP was surprisingly unaffected. These results suggest that in MDCK cells, endocytic organelles contain a BFA-sensitive coat that regulates their organization and function even though the Golgi coat is BFA resistant.
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510.
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Hunziker
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JA
Whitney
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I
Mellman
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D020126:Brefeldin A; D002417:Cattle; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D003517:Cyclopentanes / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects; D004848:Epithelium / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006056:Golgi Apparatus / Q000187:drug effects; D007070:Immunoglobulin A / Q000378:metabolism; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000378:metabolism; D008854:Microscopy, Electron; D008870:Microtubules / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism; D011971:Receptors, Immunologic; D012635:Secretory Component / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism
D003517:Cyclopentanes; D007070:Immunoglobulin A; D008562:Membrane Glycoproteins; D011961:Receptors, Fc; D011971:Receptors, Immunologic; D012635:Secretory Component; D014168:Transferrin; D020126:Brefeldin A