STRIPAK complex defects result in pseudosexual reproduction in Cryptococcus neoformans

Abstract

STRIPAK is an evolutionarily conserved signaling complex that coordinates diverse cellular processes across fungi and animals. In the human fungal pathogen Cryptococcus neoformans, STRIPAK was recently shown to play critical roles in maintaining genome stability and controlling both sexual and asexual development. In Cryptococcus, sexual reproduction is closely linked to virulence, and our findings demonstrate that the STRIPAK complex plays key roles in both processes. Here, we further investigate the specific roles of the STRIPAK catalytic subunit Pph22 and its regulatory partner Far8 during sexual development. We show that while pph22{Delta} mutants are defective in -a sexual reproduction, exhibiting impaired meiotic progression and a failure to produce viable spores, the deletion of PPH22 resulted in exclusive pseudosexual reproduction, with progeny inheriting nuclear genomes solely from the wild-type parent. Overexpression of PPG1, a related phosphatase, rescued growth and developmental defects in pph22{Delta} mutants, and restored the preference for -a sexual reproduction over pseudosexual reproduction during mating, suggesting functional redundancy within the STRIPAK signaling network. Furthermore, deletion of FAR8, another component of the STRIPAK complex, also led to a high rate of pseudosexual reproduction during -a sexual mating, reinforcing the role of STRIPAK in modulating reproductive modes in C. neoformans, possibly through regulating nuclear inheritance and meiotic progression. Together, these findings highlight the distinct contributions of STRIPAK to sexual reproduction in C. neoformans and suggest that disruptions of this complex affect genome integrity and inheritance mechanisms, with broader implications for fungal adaptation and pathogenesis.