Peptide-receptor signaling in plant-microbe interactions - PROJECT SUMMARY Host-microbe interactions are ubiquitous in nature and central to health and disease, growth and development, and ecosystem functioning, and range from mutualistic to parasitic. To avoid disease but allow interactions with beneficial microbes, hosts must perceive external inputs, decode and `decide' between multiple signals, and trigger an appropriate response. This concept is referred to as `cellular decision-making'. Furthermore, some microbes express molecules resembling those of the host, which hijack host signaling mechanisms and modulate host cellular decision-making for their own benefit. This process is called `molecular mimicry'. Here, the following fundamental questions will be addressed: How do cells make unique decisions based on diverse environmental inputs? How do cells distinguish between closely related, yet specific signaling molecules to elicit a unique response? How do microbial molecules interfere with host decision-making? These questions will be addressed in a mutualistic host-microbe model: plant interactions with arbuscular mycorrhizal fungi (AMF). In this system, beneficial AMF form symbiotic structures within living root cortex cells, requiring tight control by the host to ensure mutualism and prevent parasitism. CLAVATA signaling is a key regulator of plant-AMF interactions, with roots colonized by AMF expressing various CLE peptides that are perceived by CLAVATA receptors. Although structurally similar and relying on an overlapping set of receptors, each CLE has a specific role in either promoting or inhibiting AMF colonization. Moreover, AMF produce CLE- like peptides that hijack host receptors to enhance microbial colonization. Thus, CLAVATA signaling in plant- AMF interactions serves as an excellent model for studying cellular decision-making and molecular mimicry. Cellular decision-making depends on the information input, which in the case of CLAVATA signaling, is encoded by CLE peptides. First, novel host and microbial CLE peptides that regulate plant-AMF interactions will be identified and functionally characterized. Once a library of CLE peptides with effect on the interaction has been established, the cellular decision-making process at the ligand-receptor interface will be investigated. Here, binding efficiency of peptide-receptor modules will be determined and amino acid residues critical for binding of a CLE-receptor module will be identified. Finally, decision outcomes will be determined by investigating specific transcriptional responses to host and microbial CLE peptides at cellular resolution. The proposed work has broad implications for our understanding of the fundamental mechanisms of ligand- receptor interactions, cellular decision-making, and microbial manipulation of host signaling. Similar mechanisms also operate during human immune responses to viruses, bacteria, and fungi. In addition, plant- AMF interactions are ubiquitous in nature and optimized use of the mutualistic relationship in agriculture should be instrumental to provide food, feed, and fuel for a growing human population.
