Efrapeptins block exocytic but not endocytic trafficking of proteins.
During the course of screening studies to identify inhibitors of intracellular protein trafficking, we isolated efrapeptins as active principles. These compounds arrested syncytium formation (SF) and cytopathic effect (CPE) in Newcastle disease virus (NDV)- and vesicular stomatitis virus (VSV)-infected BHK cells, respectively, without profoundly affecting glycoprotein synthesis. Efrapeptins blocked cell surface expression of NDV-HN and VSV-G glycoproteins, but did not suppress intoxication by ricin or diphtheria toxin even after prolonged pretreatment. Efrapeptins are inhibitors of F-ATPase, or ATP synthase, but their inhibitory effect on SF and CPE was independent of the amount of intracellular ATP.
Muroi
M
M
Animal and Cellular Systems Laboratory, Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
Kaneko
N
N
Suzuki
K
K
Nishio
T
T
Oku
T
T
Sato
T
T
Takatsuki
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D006224:Cricetinae; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004167:Diphtheria Toxin / Q000633:toxicity; D004705:Endocytosis / Q000187:drug effects*; D005089:Exocytosis / Q000187:drug effects*; D015726:Giant Cells; D008856:Microscopy, Fluorescence; D009522:Newcastle disease virus / Q000187:drug effects / Q000502:physiology; D010455:Peptides; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012276:Ricin / Q000037:antagonists & inhibitors / Q000633:toxicity; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000502:physiology; D014764:Viral Proteins / Q000096:biosynthesis
D000900:Anti-Bacterial Agents; D004167:Diphtheria Toxin; D010455:Peptides; D014764:Viral Proteins; C012953:efrapeptin; D000255:Adenosine Triphosphate; D012276:Ricin; D006180:Proton-Translocating ATPases