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Accumulation of specific sterol precursors targets a MAP kinase cascade mediating cell–cell recognition and fusion

2016; National Academy of Sciences; Volume: 113; Issue: 42 Linguagem: Inglês

10.1073/pnas.1610527113

1091-6490

Martin Weichert, Alexander Lichius, Bert-Ewald Priegnitz, Ulrike Brandt, Johannes Gottschalk, Thorben Nawrath, Ulrike Groenhagen, Nick D. Read, Stefan Schulz, André Fleißner,

Microbial Natural Products and Biosynthesis

Significance Deficiencies in sterol biosynthesis resulting in the accumulation of precursor sterol molecules are commonly associated with cellular malfunctioning and disease, including neurodegenerative and inflammatory disorders. However, the molecular and cellular consequences of the aberrant accumulation of sterol precursors are not understood. In particular, it is unclear whether specific biochemical or signaling pathways are targeted by the precursors and to what extent their specific structures contribute to their disruptive effects. Here we show that the accumulation of ergosterol precursors specifically targets a conserved ERK MAP kinase pathway that mediates fungal cell–cell communication and fusion. This effect is only caused by precursors with a conjugated double bond in their aliphatic side chain, indicating specific structure–function relationships in the mechanism of action.