Hsp90 interaction networks in fungi—tools and techniques

Abstract

Heat-shock protein 90 (Hsp90) is a central regulator of cellular proteostasis. It stabilizes numerous proteins that are involved in fundamental processes of life, including cell growth, cell-cycle progression and the environmental response. In addition to stabilizing proteins, Hsp90 governs gene expression and controls the release of cryptic genetic variation. Given its central role in evolution and development, it is important to identify proteins and genes that interact with Hsp90. This requires sophisticated genetic and biochemical tools, including extensive mutant collections, suitable epitope tags, proteomics approaches and Hsp90-specific pharmacological inhibitors for chemogenomic screens. These usually only exist in model organisms, such as the yeast Saccharomyces cerevisiae . Yet, the importance of other fungal species, such as Candida albicans and Cryptococcus neoformans , as serious human pathogens accelerated the development of genetic tools to study their virulence and stress response pathways. These tools can also be exploited to map Hsp90 interaction networks. Here, we review tools and techniques for Hsp90 network mapping available in different fungi and provide a summary of existing mapping efforts. Mapping Hsp90 networks in fungal species spanning >500 million years of evolution provides a unique vantage point, allowing tracking of the evolutionary history of eukaryotic Hsp90 networks.

Aspergillus fumigatus escape mechanisms from its harsh survival environments

“…Hsp90 is a conserved and essential eukaryotic molecular chaperone; it mediates proteostasis to avoid protein damage and misfolding during hyperthermy (Hervás and Oroz 2020). Hsp90 also interacts with cell wall integrity pathway (CWIP) components which are crucial signaling pathways maintaining cell viability under thermal stress (Crunden and Diezmann 2021). With the temperature increase, Hsp90 could interact with the CWIP component MAPK to prevent its aggregation (Rocha and Minari 2021).…”

Insights and Perspectives on the Role of Proteostasis and Heat Shock Proteins in Fungal Infections

“…In an ex vivo nail infection model, Hsp90 inhibition affected the ability of T. rubrum to degrade keratin [ 89 ] and reduced its growth and virulence [ 11 ]. Overall, Hsp90 articulates morphological and stress-associated programs that promote virulence in different fungal pathogens [ 48 , 146 , 147 , 148 ].…”

Hsp90: From Cellular to Organismal Proteostasis

“…Hsp90 assists with the general folding and stabilization of proteins that are under stress, thus maintaining proteostasis and cell survival [ 29 ]. In human cells, it was estimated that 60% of the kinases are dependent on Hsp90 [ 30 ].…”