Brefeldin A causes a microtubule-mediated fusion of the trans-Golgi network and early endosomes.
Brefeldin A (BFA) is a fungal metabolite that causes a redistribution of the stacked cisternae of the Golgi complex into the endoplasmic reticulum by inhibiting anterograde transport. We report that BFA also causes membrane tubules derived from the trans-Golgi network (TGN) to fuse with early endosomes. In the presence of BFA, a mannose-6-phosphate receptor (M6PR)-enriched tubular network rapidly forms from the TGN, not from the prelysosomal compartment, and can be labeled with endocytic tracers after only 5 min of uptake at either 20 degrees C or 37 degrees C, indicating that it is also functionally an early endosome. Formation of the TGN-early endosome network is microtubule dependent and may involve modification of membrane processes affected by microtubule-associated motor activity. Concomitant with the formation of the fused TGN-early endosome network, there is a greater than 5-fold increase in cell surface M6PRs. The data suggest that BFA has revealed a membrane transport cycle between the TGN and early endosomes, perhaps used for the secretion or delivery of molecules to the cell surface.
Wood
S A
SA
Section of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, New York 14850.
Park
J E
JE
Brown
W J
WJ
D000818:Animals; D020126:Brefeldin A; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003517:Cyclopentanes / Q000494:pharmacology*; D004285:Dogs; D004705:Endocytosis; D005455:Fluorescent Antibody Technique; D006056:Golgi Apparatus / Q000187:drug effects*; D007425:Intracellular Membranes / Q000187:drug effects / Q000648:ultrastructure; D008561:Membrane Fusion / Q000187:drug effects*; D008854:Microscopy, Electron; D008870:Microtubules / Q000502:physiology*; D009081:Mucolipidoses / Q000503:physiopathology; D051381:Rats; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000378:metabolism
D003517:Cyclopentanes; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; D020126:Brefeldin A