エジプトヤブカHsp70は酸化的ストレス下でATPアーゼ活性とタンパク質保護が強化される

Aedes aegypti mosquitoes are responsible for transmitting several viral diseases in humans, including Dengue, Zika, Yellow Fever, and Chikungunya. Despite significant efforts to control the mosquito vector and the viruses, the issue has intensified. This is mainly due to the mosquito's successful adaptation to urban environments and its expanding geographic range, driven by rising global temperatures. To effectively combat vector-borne diseases, we need a comprehensive understanding of mosquito physiology and cellular regulatory mechanisms, as these could reveal new molecular targets for intervention. A major cellular threat is environmental stress, which can cause protein misfolding and aggregation, ultimately leading to cell death. To counteract this, cells utilize their Protein Quality Control (PQC) system to maintain proteostasis. A central component of this system is the Hsp70 chaperone family, which is crucial for nascent protein folding, translocation across membranes, refolding of aggregated proteins, targeting proteins for degradation, and providing general stress protection. In this context, we identified, cloned, expressed, and characterized a cytosolic Hsp70 homolog from Aedes aegypti, which we named AaHsp70. The recombinant AaHsp70 protein was obtained in a pure and folded form, functioning as a monomer in solution and exhibiting hallmark features of the Hsp70 family, including ATPase activity and chaperone function. Notably, its ATPase activity was 2.5 to 3.3 times higher than that of human Hsp70s and increased by 90% under oxidative conditions. Furthermore, AaHsp70 successfully protected several proteins from aggregation under redox stress in Aedes larval cell extracts. Among the protected proteins was actin, a crucial cytoskeletal and contractile protein involved in both larval and adult muscle function in insects. Overall, our findings demonstrate that AaHsp70 plays a vital role in maintaining protein homeostasis under stress in mosquito cells. This chaperone may represent a promising molecular target for developing novel strategies to mitigate the spread of Aedes aegypti and the diseases it transmits.