Effects of rhizopodin and latrunculin B on the morphology and on the actincytoskeleton of mammalian cells

The effects of the novel myxobacterial compound rhizopodin on mammalian cel ls were studied and compared with those of latrunculin B. Both substances i nduced adherently growing L929 mouse fibroblasts and PtK2 potoroo kidney ce lls to produce long, narrow, branched extensions or runners. Rhizopodin was more efficient than latrunculin B in that respect (minimal inhibitory conc entration with L929 cells 5 nM vs 50 nM), and, in contrast to latrunculin B , its effects were permanent. Rhizopodin-treated cells became much larger t han normal cells and were multinucleate, yet stayed alive and biochemically active for several weeks. Latrunculin B-treated cells returned to a quasi- normal state within 3-4 days. But latrunculin B acted faster, with the firs t effects becoming visible almost immediately upon the addition of the drug , while the first rhizopodin effects were seen 10 min later. Both substance s caused reorganization of the actin cytoskeleton. When 100 nM rhizopodin w as added to PtK2 cells, the stress fibers began to decay after just 10 min and had disappeared completely after about 3 h. Later there was a gradual r estitution of F-actin. Long F-actin fibers were seen within the runners, an d only there; in fact, these fibers may be responsible for the development and extension of the runners. The microtubuli network adjusted itself to th e new cell morphology, but was not directly impaired by the compound.