Calcineurin Targets Involved in Stress Survival and Fungal Virulence

• DOI: 10.1371/journal.ppat.1005873
• Publication Date: 2016-09-09T18:26:15Z
• Authors: Hee-Soo Park; Eve W. L. Chow; Ci Fu; Erik J. Soderblom; M. Arthur Moseley; Joseph Heitman; Maria E. Cardenas
• Keywords: Proteomics; 570; 0303 health sciences; Virulence; QH301-705.5; Calcineurin; Saccharomyces cerevisiae; RC581-607; Phosphoproteins; 3. Good health; Fungal Proteins; 03 medical and health sciences; Stress, Physiological; Cryptococcus neoformans; Animals; Humans; RNA, Messenger; Immunologic diseases. Allergy; Biology (General); Research Article; Transcription Factors

Calcineurin governs stress survival, sexual differentiation, and virulence of the human fungal pathogen Cryptococcus neoformans. is activated by increased Ca2+ levels caused stress, transduces signals dephosphorylating protein substrates. Herein, we identified characterized calcineurin substrates in C. neoformans employing phosphoproteomic TiO2 enrichment quantitative mass spectrometry. The targets include transactivator Crz1 as well novel whose functions are linked to P-bodies/stress granules (PBs/SGs) mRNA translation decay, such Pbp1 Puf4. We show that a bona fide substrate, localization transcriptional activity controlled calcineurin. previously demonstrated thermal other stresses trigger PBs/SGs. Several localized PBs/SGs, including Puf4 Pbp1, contribute resistance individually or conjunction with Crz1. Moreover, also required for development. Genetic epistasis analysis revealed Lhp1, Puf4, function branched pathway orchestrates survival virulence. These findings support model whereby controls virulence, at level via Crz1, post-transcriptionally localizing PBs/SGs acting on involved metabolism. this study share little overlap known substrates, exception In particular, binding proteins residents comprise cohort have not been mammals Saccharomyces cerevisiae. This suggests either extensive evolutionary rewiring pathway, alternatively these yet be organisms. further highlight an outstanding define calcineurin-responsive networks antifungal therapy.