title: Phospholipase D stimulation is required for sphingosine-1-phosphate activation of actin stress fibre assembly in human airway epithelial cells.
abstract: In human airway epithelial cells, sphingosine-1-phosphate (SPP) and lysophosphatidic acid (LPA) stimulated the production of phosphatidic acid (PA), which was inhibited by the primary alcohol butan-1-ol, but not by the inactive butan-2-ol, clearly indicating phospholipase D (PLD) involvement. Both SPP and LPA stimulated actin stress fibre formation, which was also butan-2-ol-insensitive and inhibited by butan-1-ol. SPP-induced PLD activation and cytoskeletal remodelling were insensitive to brefeldin A and toxin B from Clostridium difficile, which conversely blocked the effect of LPA, suggesting that the monomeric GTPases ADP ribosylation factor (ARF) and Rho are involved in LPA, but not in SPP responses. Pertussis toxin inhibited SPP- but not LPA-induced effects. PLD activation and stress fibre formation by both lysolipids were abolished by the tyrosine kinase inhibitor genistein. Addition of PA to cells caused a massive stress fibre assembly. In conclusion, PLD is one of the signalling components linking SPP-receptor activation to assembly of actin stress fibres.
authors.affiliation: Dipartimento di Biologia Evoluzionistica Sperimentale, Università di Bologna, Via Irnerio 42, 40126 Bologna, Italy.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Porcelli
authors.forename: Anna
authors.initials: A
authors.lastname: Ghelli
authors.forename: Silvana
authors.initials: S
authors.lastname: Hrelia
authors.forename: Michela
authors.initials: M
authors.lastname: Rugolo
mesh_terms: D020001:1-Butanol / Q000494:pharmacology; D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism*; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000494:pharmacology; D020126:Brefeldin A / Q000494:pharmacology; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007700:Kinetics; D008246:Lysophospholipids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D037342:Pertussis Toxin; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology*; D020033:Protein Isoforms / Q000378:metabolism; D020545:Respiratory Mucosa / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D022502:Stress Fibers / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D000199:Actins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D008246:Lysophospholipids; D020033:Protein Isoforms; D010566:Virulence Factors, Bordetella; C031815:toxB protein, Clostridium difficile; D020126:Brefeldin A; C060506:sphingosine 1-phosphate; D020001:1-Butanol; D037342:Pertussis Toxin; D010739:Phospholipase D; D013110:Sphingosine