Apical endocytosis of ricin in MDCK cells is regulated by the cyclooxygenase pathway.
Addition of arachidonic acid or stimulation of arachidonic acid production by secretory phospholipase A2 selectively upregulated apical endocytosis of ricin in MDCK cells without affecting basolateral endocytosis. Electron microscopic studies revealed that MDCK cells treated with secretory phospholipase A2 and incubated with horseradish peroxidase had an increased number of normal appearing peroxidase-labeled endosomes and no sign of membrane ruffling. Moreover, inhibition of basal arachidonic acid release, either by decreasing the cytosolic phospholipase A(2) activity or the diacylglycerol lipase activity, reduced the rate of apical endocytosis. Furthermore, indomethacin, an inhibitor of the cyclooxygenase pathway, counteracted the stimulation of endocytosis seen with both secretory phospholipase A2 and arachidonic acid, suggesting that formation of eicosanoids such as prostaglandins could be essential for the regulation. This idea was supported by the finding that prostaglandin E2, the predominant prostaglandin formed in kidney, also upregulated ricin uptake. The regulatory effect of the cyclooxygenase pathway on apical endocytosis of ricin was found to be independent of protein kinases A and C, which are known to selectively control apical clathrin-independent endocytosis in polarized cells.
Llorente
A
A
Institute for Cancer Research at The Norwegian Radium Hospital, Montebello, Norway.
van Deurs
B
B
Garred
O
O
Eker
P
P
Sandvig
K
K
D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D001095:Arachidonic Acids / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D003512:Cyclohexanones / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D015759:Ionomycin / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D063065:Organophosphonates; D010455:Peptides; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000494:pharmacology; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D012276:Ricin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014862:Wasp Venoms / Q000494:pharmacology
D001095:Arachidonic Acids; D003512:Cyclohexanones; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D016859:Lipoxygenase Inhibitors; D063065:Organophosphonates; D010455:Peptides; D011453:Prostaglandins; D014862:Wasp Venoms; C104810:methyl arachidonylfluorophosphonate; D016718:Arachidonic Acid; D000001:Calcimycin; D015759:Ionomycin; C037500:mastoparan; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; D012276:Ricin; D011451:Prostaglandin-Endoperoxide Synthases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010741:Phospholipases A; D008071:Lipoprotein Lipase; D054467:Phospholipases A2; D020962:Heterotrimeric GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate