Cytoplasmic phospholipase A2 antagonists inhibit multiple endocytic membrane trafficking pathways.
Previous studies have suggested a role for cytosolic Ca(2+)-independent phospholipase A(2) (PLA(2)) activity in the formation of endosome membrane tubules that participate in the export of transferrin (Tf) and transferrin receptors (TfR) from sorting endosomes (SEs) and the endocytic recycling compartment (ERC). Here we show that the PLA(2) requirement is a general feature of endocytic trafficking. The reversible cytoplasmic PLA(2) antagonist ONO-RS-082 (ONO) produced a concentration-dependent, differential block in the endocytic recycling of both low-density lipoprotein receptor (LDLR) and TfRs, and in the degradative pathways of LDL and epidermal growth factor (EGF). These results are consistent with the model that a cytoplasmic PLA(2) plays a general role in the export of cargo from multiple endocytic compartments by mediating the formation of membrane tubules.
Doody
Anne M
AM
Department of Molecular Biology and Genetics, Cornell University, Biotechnology Building, Ithaca, NY 14853, USA.
Antosh
Amy L
AL
Brown
William J
WJ
D062365:Aminobenzoates / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002723:Chlorobenzoates; D002934:Cinnamates / Q000494:pharmacology; D003593:Cytoplasm / Q000201:enzymology*; D004705:Endocytosis / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D054510:Phospholipases A2, Cytosolic / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism*; D062367:ortho-Aminobenzoates
D062365:Aminobenzoates; D002723:Chlorobenzoates; D002934:Cinnamates; D010726:Phosphodiesterase Inhibitors; D011973:Receptors, LDL; D011990:Receptors, Transferrin; D062367:ortho-Aminobenzoates; D004815:Epidermal Growth Factor; C060048:2-(4-amylcinnamoyl)amino-4-chlorobenzoic acid; D054510:Phospholipases A2, Cytosolic
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