Novel Ser74 of NF-κB/ Cg IκBα Phosphorylated by MAPK/ERK Regulates Temperature Adaptation in Oysters

Phosphorylation of IκBα at Ser32 and Ser36 by IKKs during biotic stress triggers its ubiquitin-proteasome degradation, causing to the nuclear translocation of REL, representing a key cascade mechanism in metazoans conserved and immune core signaling pathway, NF-κB. However, studies on its response to abiotic stress and signal transduction by phosphorylation in mollusks are lacking. Here, we firstly report a novel heat-induced phosphorylation site (Ser74) at the major NF-κB/ Cg IκBα of oysters, phosphorylated by MAPK/ Cg ERK1/2, which independently mediated the subsequent ubiquitin-proteasome degradation without phosphorylation at Ser32 and Ser36 and decreased thermal stability. The degradation of Cg IκBα promoted Cg REL nuclear translocation, which stimulated cell survival related gene expression to defend against thermal stress. The MAPK and NF-κB pathways exhibited stronger activation patterns in higher environmental temperature and in the warm-adapted Crassostrea angulata than those in the cold-adapted C. gigas -two allopatric congeneric oyster species with differential habitat temperatures. These findings unveil the complex and unique phosphorylation-mediated signal transduction mechanisms in marine invertebrates, and further expand our understanding of the evolution and function of established classical pathway crosstalk mechanisms.