MAPK/ERK-driven transcriptional regulation mediates divergent thermal tolerance in two congeneric oyster species

Abstract

Oysters, globally distributed filter-feeding bivalves, are ecologically and economically vital, yet summer mass mortality events due to global warming threaten their sustainable development. ERK1/2 function as a phosphorylation-activated molecular switch in MAPK pathway, transducing thermal stress signals via nuclear translocation and transcription factor interaction to regulate thermotolerance-related genes expression in oysters. In this study, we comprehensively investigated the transcriptional regulatory role of ERK kinase in oyster thermotolerance through combined treatment with ERK kinase inhibitors and heat stress, integrated with RNA-Seq and physiological/biochemical assays. Our data demonstrate that ERK, under heat stress, activated phagocytosis (Drpr, Sqstm1), coordinated intricate pathway cross-talk among PI3K-AKT pathway, mTOR pathway, and NF-ĸB signaling pathway (Fos, Trpm2, Pik3ca), inhibited apoptosis (Birc3, Bax, Bcl-2), and optimizing energy conversion processes (HK, PK, C1qtnf3, Fasn). The integrated transcriptomic analysis of Crassostrea gigas and Crassostrea angulata further confirmed the critical role of ERK-regulated genes in thermal adaptation. This study elucidates the transcriptional regulation network of MAPK/ERK pathway in oyster thermotolerance, and advancing our mechanistic understanding of heat resilience in marine invertebrates. Meanwhile, the identified molecular regulators provide actionable targets for breeding heat-resistant oyster strains, offering a dual foundation for both ecological conservation and sustainable oyster aquaculture in the context of global warming.