FIGURE 9.

Proposed model for DspA/E-induced toxicity. DspA/E requires Cdc55-PP2A activity to induce dephosphorylation of Orm proteins as shown by analysis of the Δcdc55 mutant. Upon Orm dephosphorylation, SPT inhibition is enhanced, which in turn leads to LCB depletion. DspA/E-induced growth arrest and alteration of cellular traffic are counteracted in sphingolipid mutants that compensate DspA/E-induced LCB depletion, indicating that it is the LCB depletion that triggers growth arrest and perturbation of cellular traffic.