Innate immunity-associated endosomes and pathogen attack in Arabidopsis PI: HE, Sheng Yang; Michigan State University Project summary The long-term goal of this research is to elucidate the vesicle trafficking network of the innate immune system and how pathogens modulate this network to cause infectious diseases. Plants and mammals share functionally analogous innate immune systems that are important for combating microbial pathogens. Despite many exciting advances over the past two decades in our understanding of plant and mammalian innate immune systems, major knowledge gaps remain in both systems. A particularly poorly understood aspect of the innate immune system is the vesicle trafficking component that controls immunity-associated receptors, signaling components, and cargoes. For the past two decades, the tractable Arabidopsis-Pseudomonas syringae pathosystem has been used to discover and characterize many innate immune regulators, as well as pathogen effectors that modulate innate immune responses. By studying the bacterial effector HopM1, the principal investigator's laboratory discovered the MIN7 protein, an Arabidopsis guanine nucleotide exchange factor (GEF) belonging to the ADP ribosylation factor (ARF) family. MIN7 is located in early endosomes that recycle plasma membrane proteins and is required for all major branches of plant innate immunity, suggesting a key role in innate immune traffic. The identification of MIN7-associated endosomes now provides an exciting entry point for gaining a comprehensive understanding of the poorly characterized recycling endosomes in immune traffic in a model eukaryotic system. In this research, an integrative approach, involving methods in molecular genetics, cell biology, biochemistry, and microbial pathogenesis, will be taken to understand MIN7-associated vesicle traffic. The specific goals of this project are: 1) to investigate MIN7 protein stability during disease and immunity, 2) to identify and characterize the components of the immune-associated MIN7 protein complex and MIN7-associated recycling endosomes, and 3) to characterize the newly discovered MIN7-associated focal immune zones (MAIZs). Elucidating the mechanisms by which MIN7 regulates innate immune traffic has the potential to illuminate the fundamental principles underlying innate immune responses. Enhanced understanding of host innate immune systems and their manipulation by microbial pathogens promises to provide fundamental knowledge for the development of novel methods of disease intervention in humans and plants.

Public Health Relevance

This application describes basic research to elucidate the vesicle trafficking network of the plant innate immune system and how pathogens modulate this network to cause infectious diseases. The knowledge gained from this research should yield broad principles for the development of novel and effective methods of disease intervention in humans and plants.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM109928-04
Application #
9398154
Study Section
Innate Immunity and Inflammation Study Section (III)
Program Officer
Somers, Scott D
Project Start
2015-01-01
Project End
2018-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
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