Brefeldin A's effects on endosomes, lysosomes, and the TGN suggest a general mechanism for regulating organelle structure and membrane traffic.
Addition of brefeldin A (BFA) to most cells results in both the formation of extensive, uncoated membrane tubules through which Golgi components redistribute into the ER and the failure to transport molecules out of this mixed ER/Golgi system. In this study we provide evidence that suggests BFA's effects are not limited to the Golgi apparatus but are reiterated throughout the central vacuolar system. Addition of BFA to cells resulted in the tubulation of the endosomal system, the trans-Golgi network (TGN), and lysosomes. Tubule formation of these organelles was specific to BFA, shared near identical pharmacologic characteristics as Golgi tubules and resulted in targeted membrane fusion. Analogous to the mixing of the Golgi with the ER during BFA treatment, the TGN mixed with the recycling endosomal system. This mixed system remained functional with normal cycling between plasma membrane and endosomes, but traffic between endosomes and lysosomes was impaired.
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
J
J
Lippincott-Schwartz
L
L
Yuan
C
C
Tipper
M
M
Amherdt
L
L
Orci
R D
RD
Klausner
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D020126:Brefeldin A; D002460:Cell Line; D020756:Coatomer Protein; D003517:Cyclopentanes / Q000494:pharmacology*; D004705:Endocytosis; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006056:Golgi Apparatus / Q000187:drug effects; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000187:drug effects* / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D015388:Organelles / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011990:Receptors, Transferrin / Q000378:metabolism; D013045:Species Specificity; D014168:Transferrin / Q000378:metabolism
D020756:Coatomer Protein; D003517:Cyclopentanes; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D011990:Receptors, Transferrin; D014168:Transferrin; D020126:Brefeldin A