Monensin inhibits synthesis of plasma membrane sphingomyelin by blocking transport of ceramide through the Golgi: evidence for two sites of sphingomyelin synthesis in BHK cells.
The monovalent cationophore monensin, which is known to interfere with vesicular transport through the Golgi apparatus, inhibits synthesis of sphingomyelin in BHK cells by up to 40%. The monensin-sensitive component of sphingomyelin synthesis appears to be the pool which normally reaches the cell surface since treatment of cells with exogenous sphingomyelinase causes an almost identical loss of sphingomyelin. Monensin causes increases in ceramide and glucosylceramide labelling which together are equivalent to the decrease in sphingomyelin labelling. Monensin also increases synthesis of cholesterol ester, probably due to the decreased delivery of sphingomyelin to the plasma membrane. However, monensin has no effect on resynthesis of plasma membrane sphingomyelin which has been degraded by extracellular sphingomyelinase. The results support the idea that synthesis of sphingomyelin destined for the plasma membrane does not occur in the cis- or medial-Golgi but depends on vesicular transport of ceramide to a second synthesis site which is distal to the medial-Golgi.
Kallen
K J
KJ
Department of Physiology, University College London Medical School, UK.
Quinn
P
P
Allan
D
D
D000818:Animals; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D006224:Cricetinae; D006017:Glycolipids / Q000378:metabolism; D006056:Golgi Apparatus / Q000187:drug effects* / Q000378:metabolism; D008985:Monensin / Q000494:pharmacology*; D013108:Sphingomyelin Phosphodiesterase / Q000494:pharmacology; D013109:Sphingomyelins / Q000096:biosynthesis*; D014316:Tritium
D002518:Ceramides; D006017:Glycolipids; D013109:Sphingomyelins; D014316:Tritium; D008985:Monensin; D013108:Sphingomyelin Phosphodiesterase; D002794:Choline