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

Award Number: R01GM120316
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary The 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 fundamental biological processes, steroid hormone signaling and autophagy, that are conserved across eukaryotes. Brassinosteroids (BRs) are plant steroid hormones that promote growth. Autophagy occurs in both plants and animals to degrade organelles and proteins, especially under stress conditions. Our preliminary work has established several interaction points between BR and autophagy pathways. First, BES1, a transcription factor mediating BR responses, is degraded by selective autophagy, mediated by the ubiquitin receptor DSK2. Furthermore, phosphorylation of DSK2 by BIN2, a negative regulator in the BR signaling pathway, increases the interaction between DSK2 and ATG8, resulting in BES1 degradation. Second, TOR, a negative regulator of autophagy, is required for BR-mediated growth, and BRs inhibit autophagy likely via BIN2 interaction with TOR. We hypothesize that BR and autophagy pathways crosstalk through multiple mechanisms to coordinate plant growth and stress responses: (a) upon phosphorylation by BIN2, DSK2 acts as a phospho-regulated autophagy receptor for BES1, and BES1 ubiquitination therefore leads to its degradation by selective autophagy. This in turn slows down plant growth under stress conditions; (b) BRs regulate TOR to promote growth and inhibit autophagy through BIN2 phosphorylation of TOR. To test and expand on these hypotheses we propose the following two Specific Aims: (1) To establish the functions of selective autophagy receptor DSK2 and E3 ubiquitin ligases BAF1 and BAR1 in mediating BES1 degradation through autophagy; (2) To determine the mechanism of BR regulation of TOR via BIN2, and the effect of this regulation on growth and autophagy under normal and stress conditions. These studies will leverage the genetic and genomic resources in Arabidopsis and use cutting-edge proteomics to study ubiquitination and phosphorylation at the individual protein and proteome-wide levels. These innovative approaches have the potential not only to reveal specific mechanisms of crosstalk between steroid signaling and protein degradation pathways, but also provide transformative concepts and information on the integration of growth and stress responses across eukaryotes. For example, autophagy is involved in many human diseases including neurodegenerative diseases (e.g. Amyotrophic Lateral Sclerosis, Parkinson's and Huntington's) and cancer. In addition, the degradation of BES1 by autophagy is reminiscent of that of β-catenin in WNT signaling and HIF2α in hypoxia responses, which play essential roles in growth, development, stress responses and disease in animals and humans. The proposed studies can therefore provide important insight into processes related to human health.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $325,530 )
2025	2025	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Biomedical Research and Research Training	000	5	1/27/2025	COMPETING CONTINUATION	$325,530
														Subtotal = $325,530

Issue Date FY: 2023 ( Subtotal = -$40 )
2023	2020	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Biomedical Research and Research Training	000	4	9/14/2023	NON-COMPETING CONTINUATION	-$40
														Subtotal = -$40

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	515 MORRILL RD, 1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Biomedical Research and Research Training	000	4	12/14/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $304,617 )
2020	2020	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	515 MORRILL RD, 1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Biomedical Research and Research Training	000	4	12/27/2019	NON-COMPETING CONTINUATION	$274,155
2020	2020	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	515 MORRILL RD, 1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Biomedical Research and Research Training	001	4	3/9/2020	NON-COMPETING CONTINUATION	$30,462
														Subtotal = $304,617

Issue Date FY: 2019 ( Subtotal = $305,036 )
2019	2019	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Biomedical Research and Research Training	000	3	12/28/2018	NON-COMPETING CONTINUATION	$305,036
														Subtotal = $305,036

Issue Date FY: 2018 ( Subtotal = $393,764 )
2018	2018	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Biomedical Research and Research Training	002	2	9/18/2018	SUPPLEMENT FOR EXPANSION	$88,326
2018	2018	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Biomedical Research and Research Training	000	2	12/20/2017	NON-COMPETING CONTINUATION	$274,894
2018	2018	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Biomedical Research and Research Training	001	2	5/15/2018	NON-COMPETING CONTINUATION	$30,544
														Subtotal = $393,764

Issue Date FY: 2017 ( Subtotal = $305,823 )
2017	2017	IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY	1350 BEARDSHEAR HALL	AMES	IA	50011	STORY	USA	Biomedical Research and Research Training	000	1	12/16/2016	NEW	$305,823
														Subtotal = $305,823

Grand Total All Awards = $1,634,730

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

Award Number: R01GM120316

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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