Study on cooperative regulation of actin cytoskeletal organization and translation initiation.

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High osmolarity or glucose deprivation causes rapid shutdowns of both actin polarization and translation initiation in yeast. As like stresses, administration of antipsychotic phenothiazines or local anesthetics causes similar responses. All these drugs have amphiphilic structures, and are able to form emulsions and permeabilize the cell membrane, indicating that the drugs have the same features as a surfactant. Consistent with this notion, surfactants induced responses similar to those of antipsychotic drugs and local anesthetics. Benzethonium chloride, a cationic surfactant, has a more potent shutdown activity than phenothiazines, whereas SDS, an anionic surfactant, transiently depolarized actin without inhibiting translation initiation, indicating that a cationic charge in the amphiphile is important for cellular shutdown. The clinical drugs and the cationic surfactants at low concentrations caused shutdown without membrane permeabilization, suggesting that these compounds and the stresses activate the shutdowns, via perturbation rather than disruption of the cell membrane.