Receptor kinase pathway signal tuning through a nontranscriptional incoherent feedforward loop.

Abstract

Cellular signaling processes can elicit powerful responses and may need to be amplified to be efficient or dampened to prevent overstimulation. Therefore, they often involve autoregulatory feedbacks. Receptor kinase signaling pathways are abundant in plants, where they convey the presence of both exogenous and endogenous ligands. Among them, endogenous CLAVATA3/EMBRYO SURROUNDING REGION (CLE) peptide signaling acts in an inherently quantitative manner to determine the size of stem cell pools and direct tissue formation. The plant-specific MEMBRANE-ASSOCIATED KINASE REGULATOR (MAKR) family proteins act downstream of receptor kinases. Among the seven family members in Arabidopsis (Arabidopsis thaliana), MAKR5 conveys CLE45 signaling downstream of the receptor kinase BARELY ANY MERISTEM 3 (BAM3). Here, we show that the distinct MAKR5 mode of action can only be fully mimicked by MAKR3, suggesting functional diversification of MAKR proteins. Moreover, we find that CLE45-stimulated and BAM3-dependent MAKR5 recruitment to the plasma membrane can be triggered independent of receptor-like cytoplasmic kinases that act downstream of BAM3 and depends on membrane charge. The CLE45-BAM3-triggered enhancement of MAKR5 production and plasma membrane association is mediated by autoregulatory feedback on MAKR5 mRNA translation, for which the 5' UTR is required. At the same time, this signal amplification is dampened through CLE45-stimulated MAKR5 phosphorylation, which inactivates MAKR5, enhances its turnover, and impinges on MAKR5 mRNA levels. In summary, our results reveal a nontranscriptional incoherent feedforward loop in which receptor kinase signaling is amplified via ligand-triggered translation of a signal enhancer's mRNA yet also balanced via ligand-triggered inactivation of the signal enhancer protein.