‘Popping the Clutch’ Novel Mechanisms Regulating

Authors: YoonDong Park Peter R Williamson

Publish Date: 2011/09/13

Volume: 173, Issue: 5-6, Pages: 359-366

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Abstract

Sexual reproduction in fungal pathogens such as Cryptococcus provides natural selection and adaptation of the organisms to environmental conditions by allowing beneficial mutations to spread However successful mating in these fungi requires a timecritical induction of signaling pheromones when appropriate partners become available Recently it has been shown that the fungus uses the transcriptional equivalent of the racing technique ‘popping the clutch’—pushing in the clutch pedal putting the car in gear revving with the gas pedal and then dropping the clutch pedal to accelerate rapidly In the same way Cryptococcus during vegetative growth constitutively matches a high rate of pheromone synthesis with a high rate of degradation to produce repressed levels of transcript Then when mating is required the fungus drops the degradative machinery resulting in a rapid induction of the pheromone Pairing with this novel regulatory cycle is a host of mitogenactivated protein kinase cascades cyclic AMPdependent and calciumcalcineurin signaling pathways that maintain these high rates of pheromone synthesis and prime downstream pathways for an effective mating response The intersection of a number of virulenceassociated traits with sexual development such as the synthesis of an immunedisruptive laccase as well as a protective polysaccharide capsule makes these rapid regulatory strategies a formidable foe in the battle against human disease

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