Purinergic signaling appears to be an ancient, conserved trait; for example, P2X receptors trace back one billion years in evolution. However, although virtually all organisms respond to extracellular ATP (eATP), canonical P2X and P2Y receptors appear absent in insects, roundworm and higher plants. Recently, the first plant, purinergic receptor, DORN1, was identified, which defines a new receptor kinase family of purinoreceptors (P2K). This receptor mediates the primary signaling response to eATP, eliciting many responses that are comparable to an animal inflammatory response. Similar to some mammalian, purinergic receptors, DORN1 appears to monitor plasma membrane association with the extracellular matrix, as well as recognition of eATP. Convergent evolution has resulted in different receptors for eATP in plants and animals but the question remains whether other components of the purinergic signaling pathway may be conserved. Preliminary results identify interesting parallels between the animal and plant eATP responses.
In Aim 1, we will seek to determine the mechanisms by which DORN1 mediates responses to eATP. For example, in both animals and plants, eATP addition triggers the production of reactive oxygen species. Recent data indicates that DORN1 directly phosphorylates NADPH oxidase (RBOHD), which is the enzyme producing ROS.
Aim 1, study 1 will focus on further defining the importance of DORN1-RBOHD interaction. Study 2 describes experiments to define the role of the DORN1 RGD binding sites, which appear to mediate interaction between the plasma membrane and extracellular matrix, analogous to the situation in mammals. DORN1 functions as part of a membrane protein complex, whose components will be identified (Study 3). Animals have multiple P2X and P2Y receptors and this is also the case in plants. Indeed, a second, putative eATP receptor, DORN2, has been identified and Specific Aim 2, Study 4 will focus on characterizing the biochemical features and functional role of this receptor. There is a significant overlap in the plant transcriptional response to eATP and a variety of biotic and abiotic stresses. Hence, it seems likely that purinergic signaling plays a variety of important roles in plants; again mirroring the diverse roles that eATP signaling plays in mammals. Experiments are described to identify additional components of the plant purinergic response pathway by characterization of mutants defective in their response to nucleotide treatment, as well as by identification of specific mutations that result in suppression of the dorn1 mutant phenotype (Study 5). The ultimate goal will be a holistic and integrated view of plant purinergic signaling, beginning with the novel P2K receptors, with definition of plant- specific and, more importantly, plant and animal conserved components. This comparative approach should broaden our knowledge of purinergic signaling in higher organisms, hopefully aiding the design of therapeutic treatments that can alleviate a wide variety of disease states associated with the response to eATP (e.g., inflammation, neurotransmission, and cardiovascular disease).

Public Health Relevance

Purinergic signaling, which regulates cellular functions, is involved in a wide variety of disease states and is the target of valuable therapeutic agents. Although virtually all organisms respond to extracellular ATP, which is part of this purinergic signaling, many lack the established P2X and P2Y receptors found in animals. Through comparison to DORN1, a unique purinergic receptor, the research described will identify conserved, common components of purinergic signaling pathways, which may be additional targets for therapy.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Molecular and Integrative Signal Transduction Study Section (MIST)
Program Officer
Koduri, Sailaja
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Missouri-Columbia
Other Basic Sciences
Earth Sciences/Resources
United States
Zip Code
Tripathi, Diwaker; Zhang, Tong; Koo, Abraham J et al. (2018) Extracellular ATP Acts on Jasmonate Signaling to Reinforce Plant Defense. Plant Physiol 176:511-523
Shang-Guan, Keke; Wang, Min; Htwe, Nang Myint Phyu Sin et al. (2018) Lipopolysaccharides Trigger Two Successive Bursts of Reactive Oxygen Species at Distinct Cellular Locations. Plant Physiol 176:2543-2556
Chen, Dongqin; Cao, Yangrong; Li, Hong et al. (2017) Extracellular ATP elicits DORN1-mediated RBOHD phosphorylation to regulate stomatal aperture. Nat Commun 8:2265
Cho, Sung-Hwan; Nguyen, Cuong The; Choi, Jeongmin et al. (2017) Molecular Mechanism of Plant Recognition of Extracellular ATP. Adv Exp Med Biol 1051:233-253