Crosstalk between brassinosteroid and autophagy pathways in the regulation of plant growth and stress responses

Iowa State University, Ames IA

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Abstract

Project Summary The long-term goal of this project is to determine how growth, development and stress responses are coordinated in Arabidopsis, a model plant with extensive genetic, genomic and proteomic resources. This will be accomplished through detailed mechanistic studies that will provide insights into the fundamental conserved biological processes of steroid hormone signaling and autophagy. Brassinosteroids (BRs) are plant steroid hormones that promote growth and development and regulate stress responses. Autophagy occurs in all eukaryotes and degrades organelles and proteins, especially under stress conditions. We have identified multiple mechanisms by which BR signaling and autophagy are coordinated, and generated a regulatory network by combining multiple types of ‘omics data. Key points of interaction between the pathways include degradation of BES1, a transcription factor mediating BR responses, by selective autophagy to reduce growth; and phosphorylation of the TORC subunit RAPTOR1B by the BR-regulated GSK3-like kinase BIN2, leading to an increase in autophagy in response to stress via a switch in TORC substrate specificity. Our new data indicate that the MAP kinase MPK6 functions downstream of BIN2 to negatively regulate autophagy, BIN2 phosphorylates ATG13 to directly regulate autophagy, and BES1 transcriptionally regulates autophagy gene expression through histone 3 lysine 27 (H3K27) methylation, by recruiting H3K27 demethylase REF6 and methyltransferase CLF. We hypothesize that BR signaling regulates autophagy to coordinate plant growth and stress responses, through multiple mechanisms including BIN2 regulation of MAPK6, TORC and ATG13 and BES1 regulation of ATG gene expression. We propose the following Specific Aims to test the hypotheses: 1) to establish the mechanisms of BIN2 and MPK6 regulation of TORC in the control of autophagy and growth; 2) to investigate how BIN2 and TOR phosphorylation of ATG13 regulates its function by mapping phosphorylation sites and mutational analyses; 3) to establish the mechanisms and network through which BES1, together with histone H3K27 demethylase REF6 and methyltransferase CLF, regulates the expression of ATG12 and other genes to control autophagy. These studies will leverage the genetic and genomic resources in Arabidopsis and use multi-omics technologies to generate and integrate information ranging from transcriptome changes to phosphorylation sites and protein-protein interactions. These innovative approaches have the potential to provide transformative knowledge on the mechanisms of integration of growth and stress responses across eukaryotes. For example, autophagy is involved in many human diseases including neurodegenerative diseases, such as Alzheimer, Parkinson and Huntington, and links with steroid hormone action are now being identified, although mechanisms remain obscure. Autophagy also plays critical roles in cancer development, and drugs that modulate autophagy and/or TORC signaling are in clinical use or under development. The proposed studies can therefore provide important insight into processes related to human health.