|
Email: mackey.86@osu.edu
Other Academic Affiliations Department of Plant Biology Summary of research in the Mackey lab
Pathogens commonly secrete molecules that manipulate the host. Pseudomonas syringae secretes effector proteins directly into the cells of plants where they perturb signaling processes. These perturbations can enhance virulence of the bacteria. However, the effector proteins can also activate the innate immune system of the plant if they are recognized. Resistance (R) proteins expressed in the plant specify perception of effector proteins. The research in this lab addresses several biologically interesting questions: 1) How is signaling in the plant perturbed by pathogen-derived effectors? 2) How do these perturbations benefit the pathogen? 3) How do R-proteins perceive these perturbations and thereby induce defenses? AvrRpm1 and AvrB are unrelated effector proteins from P. syringae that each induce defenses on plants expressing RPM1 (an R-protein) or enhance bacterial virulence on plants lacking RPM1 (rpm1). How AvrRpm1 and AvrB induce these disparate outcomes is one major focus of the lab. AvrRpm1 and AvrB specifically target the Arabidopsis protein RIN4 (RPM1-interacting protein 4, Mackey et al., 2002). Each effector physically associates with and induces phosphorylation of RIN4. It is hypothesized that AvrRpm1 and AvrB enhance bacterial virulence by signaling through RIN4. As indicated by its name, RIN4 also interacts with RPM1. RIN4 is required for both accumulation of the RPM1 protein and for its function. It is hypothesized that AvrRpm1 and AvrB trigger RPM1-induced defenses by signaling through RIN4. We are currently testing each of these hypotheses at the molecular level. We have also shown that AvrRpt2, a third type III effector that is unrelated to AvrRpm1 or AvrB, also targets RIN4 (Mackey et al., 2003). AvrRpt2 induces the post-transcriptional disappearance RIN4, and this effect is independent of the presence of RPS2, the Arabidopsis R protein that senses AvrRpt2. RIN4 over-expression inhibits multiple phenotypes associated with AvrRpt2 function. Conversely, disruption of RIN4 results in RPS2-dependent lethality. RPS2 and RIN4 physically associate in the plant. We suggest that RIN4 is the target of the AvrRpt2 virulence function, and perturbation of RIN4 activates RPS2. A second major focus of the lab is to understand, at the molecular level, how AvrRpt2 perturbs signaling in the plant. Thus, RIN4 is a point of convergence for the activity of at least three unrelated P. syringae type III effectors. This convergence indicates that RIN4 and the plant signaling that it regulates is an important virulence target in the plant. The presence of two R-proteins (RPM1 and RPS2) dedicated to resisting pathogens that manipulate this target, furthers supports this notion. We are interested in the targets of other effector proteins, not known to target RIN4. Do these effectors target other components of the same signaling system, or do they have truly distinct virulence targets? Attempts to answer this question for a variety of effector proteins constitutes a third major focus of the lab. Our specific research questions are hypothesis driven, and the results are held to rigorous standards of interpretation. To address these questions we use techniques ranging from molecular biology and reverse genetics to cell biology, genetic, biochemical, and proteomic approaches. We will elucidate molecular mechanisms by which effector proteins enhance virulence and by which the innate immune system perceives and responds to these effectors. Within the plant-microbe community, this work will provide seminal examples of each of these processes. In the larger community, this work will enlighten, and possibly lead directly to, similar work studying effectors from animal pathogens. It will also advance the collective understanding of innate immunity resulting from comparisons across kingdoms. Relevant Publications Holt, B. F., D. Mackey, and J. L. Dangl. 2000. Primer - Recognition of Pathogens by Plants. Curr. Biol. 10: R5-R7. Mackey, D., B. Holt, A. Wiig, and J. Dangl. 2002. RIN4 Interacts with Pseudomonas syringae Type III Effector Molecules and Is Required for RPM1-Mediated Resistance in Arabidopsis. Cell 108: 743-754. Mackey, D., Belkhadir, Y., Alonso, J. M., Ecker, J. R., and Dangl, J. L. 2003. Arabidopsis RIN4 Is a Target of the Type III Virulence Effector AvrRpt2 and Modulates RPS2-Mediated Resistance. Cell 112: 379-389. Mackey, D. 2004. Plant-Targets of pathogenic effectors can transduce both virulence and resistance signals. In Vitro Cellular and Development Biology - Plant 40: 251-255. Belkhadir, Y., Nimchuk, Z., Hubert, D. A., Mackey, D., and Dangl, J. L. 2004. Arabidopsis RIN4 Negatively Regulates Disease Resistance Mediated by RPS2 and RPM1 Downstream or Independent of the NDR1 Signal Modulator and Is Not Required for the Virulence Functions of Bacterial Type III Effectors AvrRpt2 or AvrRpm1. Plant Cell 16: 2822-2835. Kim MG, da Cunha L, McFall AJ, Belkhadir Y, DebRoy S, Dangl JL, Mackey D. 2005. Two Pseudomonas syringae type III effectors inhibit RIN4-regulated basal defense in Arabidopsis. Cell. In Press.
Last modified: 5/7/2008 |
Website Administrator:
Dr. Tim Rhodus
Department of Horticulture and Crop Science
Email: rhodus.1@osu.edu