The ACBP1-RAP2.12 signalling hub: A new perspective on integrative signalling during hypoxia in plants

Abstract

During their lifetime, plants are frequently exposed to a variety of stresses which negatively impact on growth and vitality. In order to respond specifically to a given stress situation, integration of multiple signal inputs is of utmost importance. Recently, we demonstrated that recognition and adaptation to low-oxygen stress requires integration of signals from energy metabolism, lipid metabolism and oxygen availability. Low oxygen which results in an energy crisis causes a shift in lipid intermediate ratios. Binding of C18:1-CoA by ACYL-COA BINDING PROTEIN 1 (ACBP1) at the plasma membrane concomitantly leads to release and nuclear accumulation of the ERFVII transcription factor RELATED TO APETALA 2.12 (RAP2.12) which is central to the activation of anaerobic metabolism during stress. Moreover, RAP2.12 protein stability is oxygen-dependently regulated and its oxidation results in degradation by the N-end rule pathway. Here, we illuminate the concept of multiple-signal integration under hypoxia and discuss signal inputs merging at the ACBP1-ERFVII signaling hub.

Keywords: ACBP; ERFVII; Oxygen sensing; acyl-CoA; energy crisis.

Figure 1.

Model of integrative signaling under hypoxia involving the ACBP1-RAP2.12 hub. (a) Under non-stress conditions, cytosolic RAP2.12 protein is constantly destabilized by the oxygen-dependent branch of the N-end rule pathway (NERP). RAP2.12 protein which is sequestered at the plasma membrane by binding to ACBP1 can escape degradation. (b) A low oxygen concentration not affecting the cellular energy status inhibits NERP activity and results in stabilization of cytoplasmic RAP2.12 protein. However, dissociation of ACBP1-bound RAP2.12 protein is prevented. Therefore, only partial activation of hypoxic transcripts is achieved. Of note, a low oxygen concentration does not necessarily lead to a low energy status as long as the flux of oxygen into the cell meets up with mitochondrial demands. In contrast, oxygen shortage, i.e., insufficient oxygen supply, will lead in either case to low energy. (c) A low energy status, e.g., caused by reduced mitochondrial ATP synthesis or high cellular metabolic activity, modifies cellular acyl-CoA levels leading to a shift in C18:1-CoA/C16:0-CoA ratios. C18:1-CoA (shown as yellow circle) binds as ligand to ACBP1 promoting the release of RAP2.12. Due to the still active NERP, only a fraction of RAP2.12 protein reaches the nucleus to activate hypoxic genes. (d) Under a low oxygen concentration that results in an energy crisis, RAP2.12 is released from ACBP1 and gets stabilized upon NERP inhibition, leading to full activation of hypoxic gene expression. Kinases activated upon (mitochondrial) ROS, calcium or ATP signals potentially phosphorylate ACBP1 thereby further affecting its affinity towards RAP2.12.