The plant hormone jasmonic acid (JA) controls diverse aspects of host immunity and development. Studies with the model plant Arabidopsis thaliana and tomato (Solanum lycopersicum) indicate that the E3 ubiquitin ligase SCFCOI1 is strictly required for transcription of jasmonate-responsive genes. JAZ (JAsmonate ZIM-domain) proteins repress the expression of jasmonate-responsive genes by interacting with the basic helix-loop-helix transcription factor MYC2. In response to a jasmonate signal, JAZ proteins are subject to SCFCOI1-mediated ubiquitination and subsequent degradation by the 26S proteasome. Binding of JAZ repressors to the F-box protein COI1 is stimulated by the JA-amino acid conjugate jasmonoyl-isoleucine (JA-Ile). Coronatine, a toxin produced by plant disease-causing pathogens, strongly promotes COI1-JAZ interactions. The proposed research will use Arabidopsis and tomato as experimental model systems to develop the hypotheses that COI1 is a receptor for JA-Ile and coronatine, and that JAZ repressor proteins determine the specificity by which SCFCOI1 controls the diversity of jasmonate-regulated processes. A combination of biochemical, genetic, and cell biological approaches will be used to address the following specific aims: 1) To determine the role of COI1 and JAZ in binding jasmonate ligands;2) To measure the endogenous level of JA-Ile and other JA-amino acid conjugates in healthy, wounded, and diseased tissues;3) To determine the physiological function of JAZ family members;4) To identify regions in the Cterminal domain of JAZ repressors that interact with COI1 and MYC2;and, 5) To determine the role of JAZ-JAZ dimerization in regulating jasmonate responses. This research will contribute broadly to an understanding of the molecular mechanisms by which lipid-derived hormones control developmental and immune function in multicellular organisms. Crosskingdom conservation of components of the jasmonate signaling cascade indicates that the research will provide insight into signaling processes that are conserved between plants and animals. The paradigm of ligand-mediated SCF-substrate recognition that has emerged from plant hormone research establishes a novel mechanism for sensing small molecules in biological systems, which may have far-reaching implications for medicine and human health, including potential new avenues for developing drugs that target E3 ubiquitin ligases in humans. The recent discovery of jasmonates as anti-cancer agents indicates further that the proposed research is relevant to the discovery of novel therapeutic agents against neoplastic disease. Finally, the work will reveal the molecular mechanism by which a pathogenic microbe co-opts signaling pathways in its eukaryotic host during disease. The proposed research on the mechanism of jasmonate signaling will contribute broadly to an understanding of how lipid-derived hormones control developmental and immune function in diverse multicellular organisms, ranging from plants to humans. The study of ligand-mediated recognition of target substrates by E3 ubiquitin ligases will provide new information on how small molecules mediate proteinprotein interactions in biological systems, which may have far-reaching implications for medicine and human health, including potential new avenues for developing drugs that target E3 ubiquitin ligases in humans.

Public Health Relevance

The proposed research will reveal the molecular mechanism by which a pathogenic microbe coopts signaling pathways in its eukaryotic host during disease, and is also relevant to the discovery of novel therapeutic agents against neoplastic disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM057795-13S1
Application #
8522074
Study Section
Cellular Signaling and Regulatory Systems Study Section (CSRS)
Program Officer
Gindhart, Joseph G
Project Start
1998-09-01
Project End
2014-08-31
Budget Start
2011-09-01
Budget End
2014-08-31
Support Year
13
Fiscal Year
2012
Total Cost
$107,818
Indirect Cost
$37,578
Name
Michigan State University
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Campos, Marcelo L; Yoshida, Yuki; Major, Ian T et al. (2016) Rewiring of jasmonate and phytochrome B signalling uncouples plant growth-defense tradeoffs. Nat Commun 7:12570
Thireault, Caitlin; Shyu, Christine; Yoshida, Yuki et al. (2015) Repression of jasmonate signaling by a non-TIFY JAZ protein in Arabidopsis. Plant J 82:669-79
Koo, Abraham J; Thireault, Caitlin; Zemelis, Starla et al. (2014) Endoplasmic reticulum-associated inactivation of the hormone jasmonoyl-L-isoleucine by multiple members of the cytochrome P450 94 family in Arabidopsis. J Biol Chem 289:29728-38
Campos, Marcelo L; Kang, Jin-Ho; Howe, Gregg A (2014) Jasmonate-triggered plant immunity. J Chem Ecol 40:657-75
Bhosale, Rahul; Jewell, Jeremy B; Hollunder, Jens et al. (2013) Predicting gene function from uncontrolled expression variation among individual wild-type Arabidopsis plants. Plant Cell 25:2865-77
Nakata, Masaru; Mitsuda, Nobutaka; Herde, Marco et al. (2013) A bHLH-type transcription factor, ABA-INDUCIBLE BHLH-TYPE TRANSCRIPTION FACTOR/JA-ASSOCIATED MYC2-LIKE1, acts as a repressor to negatively regulate jasmonate signaling in arabidopsis. Plant Cell 25:1641-56
Herde, Marco; Koo, Abraham J K; Howe, Gregg A (2013) Elicitation of jasmonate-mediated defense responses by mechanical wounding and insect herbivory. Methods Mol Biol 1011:51-61
Moreno, Javier E; Shyu, Christine; Campos, Marcelo L et al. (2013) Negative feedback control of jasmonate signaling by an alternative splice variant of JAZ10. Plant Physiol 162:1006-17
Koo, Abraham J K; Howe, Gregg A (2012) Catabolism and deactivation of the lipid-derived hormone jasmonoyl-isoleucine. Front Plant Sci 3:19
Erb, Matthias; Meldau, Stefan; Howe, Gregg A (2012) Role of phytohormones in insect-specific plant reactions. Trends Plant Sci 17:250-9

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