FERONIA: A Malectin-Domain Receptor Kinase with Intricate Signaling Mechanisms and Profound Importance to Plant Wellness

A Receptor Kinase-GPI-AP Coreceptor Pair

FER partners with a GPI-AP from the LRE-like GPI-AP (LLG)/LORELEI (LRE) protein family as a co-receptor [39,40]. FER is expressed almost ubiquitously except in pollen grains, the specialized sperm-bearing male cells, where FER homologs are present. The four members of the LLG/LRE protein family are differentially expressed [43]. LLG1 is expressed in vegetative tissues, including in the stigma where pollen grains are deposited (Box 1). LRE is expressed in the paired synergid cells that gate the female gametophyte, located inside the ovule, where fertilization takes place. LLG2 and LLG3 are exclusively expressed in the pollen; they partner with FER counterparts in pollen grains to ensure pollen tube arrival at the ovule for fertilization [44,45]. The expression of LLG1 and LRE together spans the expression spectrum of FER. The biological activity of these LLG/LRE are interchangeable [43]. The FER-LLG1/LRE partnership was discovered because phenotypes of loss-of-LLG1 and those of loss-of-LRE mutants span the full spectrum of knockout fer mutants during growth and reproduction, respectively [40]. fer and knock-out llg1 plants are highly pleiotropic during growth and defective in the female ability to maintain mating barriers in the stigma (Box 1), to prevent penetration by unwanted pollen from incompatible plants [46-48]. Fertilization occurs in germ cells inside the female gametophyte (Box 1), and is blocked in knockout fer and lre mutants, severely suppressing female fertility. FER and LRE, acting as coreceptors, are both required to create an environment that induces sperm release from the penetrating pollen tube [49] (Box 1). Several recent reviews have discussed these FER-LLG1/LRE control phenomena comprehensively [13,18,50].

GPI-APs as Chaperones Delivering FER to its Functional Location in the Plasma Membrane

GPI-AP proteins are secreted to the cell surface where many remain linked to the outer leaflet of the plasma membrane via its GPI-anchor. They are conserved through protozoa to animals and plants, playing important roles in a wide range of processes, including development, immunity, and interacting with regulators to orchestrate signaling from the cell surface [51-57]. Much is still to be elucidated on how GPI-APs execute these functions. They exit the ER-Golgi in vesicles already destined for localization in sterol and sphingolipid-enriched subdomains of the plasma membrane. Referred to as “lipid-rafts” or micro/nanodomains [58-63] and segregated from the bulk-phase membrane, these sterol and sphingolipid-enriched membrane subdomains are specialized for orchestrating signaling from the cell surface. FER and LLG1 interact in the ER with LLG1 binding to an extracellular juxta membrane (exJM) region of FER (Figure 1A) [40]. However, in the llg1 knock-out mutants, while FER is still notably present in the plasma membrane, much of it is trapped in the ER. Clearly, the plasma membrane-located FER, presumably secreted there via the default secretory pathway, is inactive, thus resulting in llg1 phenocopying fer during the vegetative growth phase. Therefore, these results suggest that only FER complexed with LLG1 is active, leading to a model whereby the pool of LLG1-bound FER is chaperoned by LLG1 by “piggybacking” onto the GPI-AP, and together they exit the ER and are trafficked to the Golgi, then LLG1-destined locations in the plasma membrane (Figure 1C). LRE apparently also functions similarly in the ovules [40].

Interaction with LLG1/LRE is clearly a bottleneck that needs to be passed to ascertain the biological roles of FER are precisely executed despite being broadly and quite abundantly expressed. Partnering with differentially expressed homologs expands the functional spectrum without engaging more elaborate regulatory mechanisms. Plasma membrane-anchored GPI-APs lack a cytoplasmic domain and, therefore, have no cytoplasmic signaling capacity. Providing a trafficking route for a receptor kinase to capacitate its signaling activity is therefore a mechanistic strategy whereby a GPI-AP exerts its impact on signaling. Given that GPI-APs are predominantly located in membrane micro/nanodomains where many regulatory molecules are believed to congregate [51-57], FER, being chaperoned to where LLG1 is located, would be in a micro-environment concentrated with regulators of diverse processes, facilitating their interactions and therefore enable FER’s extraordinarily broad biological roles.

RALF1-FER-LLG1: A Prototypical Ligand-coreceptor Complex for FER Family Receptor Kinases

RALFs are secreted peptides discovered in the early 1980s and are noted for their growth inhibitory activities and conservation across plant species [64,65]. RALF1 were identified as a ligand of FER. It triggered phosphorylation of FER and of the growth regulatory H⁺-ATPase AHA2, and displayed FER-dependent root growth inhibition activity [66]. RALF23 was shortly determined to also bind FER to regulate FLS2-mediated immunity signaling [26]. In the tertiary ligand-coreceptor structure, an N-terminal 17-amino acid fragment from RALF23 interacts directly with the pollen-expressed LLG2, which closely mimics LLG1 in structural and biological interactions [43,67] (see Figure 1B).

We shall use RALF1-FER-LLG1 here as prototypical of the broader FER-related signaling modules. RALF1 and a majority of the RALFs are produced as pre-pro-peptides, and the mature peptides are secreted to the apoplast (the intercellular space between plant cells occupied by the cell wall matrix and freely diffusing molecules) [64,65]. Typically, Arabidopsis RALF expression is not highly specific and multiple RALFs are co-expressed to various levels in the same cell and tissue types [44,65]. Multiple RALFs could target the same coreceptor pairs, ensuring RALF availability to FER allowing it to function across the spectrum of its broad expression profile. Mature RALF1 has 59 amino acid residues, including two pairs of cysteine residues. Except for a short N-terminal region, which assumes an α-helix (Figure 1B) and includes several amino acid residues that are conserved and required for its activity to alkalinize the extracellular space, the rest of RALF1 is intrinsically disordered [64-67]. These properties are shared by most RALFs. The propensity of intrinsically disordered regions to engage in multivalent interactions [68] contributes to how RALF1 participates in FER-LLG1 signaling [69].

FER-LLG1-ROP to ROS Signaling Pathway: a Coreceptor – RHO GTPase-NADPH Oxidase Signaling Module

ROPs are a family of small GTPases closely related to animal Rac/Rho GTPases and major signaling hubs for many distinct extracellular signals and control diverse cytoplasmic pathways using a variety of effectors [70,71]. Their activity is regulated by GEFs, referred to as ROP-GEFs, switching them from the GDP-bound inactive form to the GTP-bound activated form. In a search of upstream regulators of ROPs, FER was found to bind ROP-GEF directly and functions as a cell surface receptor to activate ROPs, which in turn recruit NADPH oxidase and stimulate ROS production (Figure 1C) [72].

The FER-LLG1 to ROS pathway operates during the vegetative growth phase to support normal seedling development, controlling polarized root hair growth and cell shape morphogenesis to generate a jigsaw puzzle-patterned leaf epidermis [40,49,72-74]. During the reproductive phase, several female tissue-expressed RALFs function with FER-LLG1 to maintain ROP-mediated ROS production as a barrier at the stigma (Box 1) [46,75]. The stigmatic gate responds to compatible pollen, which downregulates the FER-LLG1-controlled pathway and relaxes the ROS-maintained barrier, allowing pollen hydration to extrude a pollen tube for penetrating the pistil. The FER-regulated pathway is stimulated by incompatible pollen, elevating the ROS environment to arrest the unwanted mates, preventing their invasion into the pistil [46-48,75]. Distinct pollen-secreted peptide ligands from compatible and incompatible pollen grains interact with the stigmatic RALF1-FER-LLG1 module to render the stigmatic environment either hospital or hostile to the courting mates.

At the final stage of pollen invasion, the pollen tube arrives at the ovule to gain entry to where the female gametes are located within the female gametophyte (Box 1). FER-LRE mediates a ROS environment to induce explosive rupture of the penetrating pollen tube, ejecting its cytoplasm and two cargo sperm cells to enable fertilization [18,49] (Box 1). Although FER is not expressed in pollen or pollen tubes, signaling modules comprised of pollen counterparts of FER and LLG1/LRE also control ROS production in pollen tubes [44,45]. There is an interesting dichotomy here: contrary to the FER-LRE maintained ROS environment that acts exogenously to weaken the cell wall and induce rupture of the invading pollen to enable fertilization, the pollen FER-LLG1 related module regulated ROS production mediates pollen tube cell wall integrity to ensure its growth until they reach the female target to achieve fertilization [18,41]. Interestingly, the FER-mediated ROS even mediates inter-kingdom communication between plant roots and its soil microbiome and regulates the level of beneficial bacteria in the rhizosphere, which in turn impacts plant wellness [34].

ROPs are major molecular switches that regulate myriad signaling pathways [70,71]. ROS are ubiquitous regulators important from cell growth to cell death and are crucial for defense responses [76,77]. In connecting FER to downstream processes, a FER-LLG1 to ROP-regulated ROS production pathway provides immense potential for signal diversification.

Further Elaborations: Linkages to Ca²⁺ and Nitric Oxide

Ca²⁺, a universal second messenger, is intimately linked to RALF-FER-LLG1/LRE signaling. RALFs trigger transient Ca²⁺ influx [64-66]. In the ovule, FER-LRE interacts with a seven transmembrane protein belonging to the Powdery Mildew resistance Locus O family, MLO7 (Figure 1C) [78]. An approaching pollen tube induces notable changes in the cytoplasmic Ca²⁺ dynamics of the synergid cells at the entrance of the female gametophyte (Box 1). MLO7 is believed to be a Ca²⁺ channel contributing to this response [79], although MLOs recruiting a cyclic nucleotide gated Ca²⁺ channel has also been noted [80]. Furthermore, the pollen tube-induced, FER-LRE-MLO7-mediated Ca²⁺ response in the synergid cells most likely involves other yet-to-be-identified Ca²⁺ channels since the contribution from MLO7 to the Ca²⁺-influx dependent sperm release process [49] is substantially weaker than from FER-LRE, leading to the suggestion that MLO7 functions as a booster to FER-LRE [81].

Nitric Oxide (NO), a gaseous signaling molecule, regulates many physiological processes in animals and plants [82-84]. It serves as a crucial mediator for FER-regulated processes [18,42,48,85]. In the stigmatic pollen barrier (Box 1), compatible pollen rapidly triggers an increase in stigmatic NO, followed by the relaxation of the FER-maintained ROS gate, allowing pollen germination and tube entry. Reversely, incompatible pollen fails to trigger a NO response, and stigmatic FER-mediated ROS remains high, blocking pollen entry. Nitroso-modified FER and NADPH oxidase together suppress the FER to ROS pathway [48]. In the ovule, along with mediating sperm release to enable fertilization [49], FER-regulated NO blocks entry by late-arriving pollen tubes when fertilization by the first penetrating pollen tube is assured, thus averting polyspermy [85] (Box 1).

Pectin

Pectin dynamics are intimately linked to RALF1-FER-LLG1 signaling [69,97] (Box 2). Two forms of pectin, methylesterified and de-esterified, mediate cell wall malleability and stiffness oppositely, rendering these polysaccharides powerful agents in regulating its dynamics. Pectin is secreted as methylesterified homogalacturonan. A battery of pectin restructuring enzymes, such as various pectinases that reduce its degree of polymerization (DP), are in the plant cell wall [90,98]. Pectin methylesterases and Pectin methylesterase inhibitors act counteractively to maintain distributions between methylesterifed and de-esterified pectins as required by the status of the cell. Methylesterified pectin is loosely associated with the wall matrix; it mediates wall malleability, accommodating cell expansion and rendering penetrability to invading agents, such as pollen tubes that grow within the cell wall matrix of female tissues (Box 1). De-esterified pectin is variably associated with the cell wall matrix. In response to cationic conditions, such as [Ca²⁺] in the wall matrix, de-esterified pectin crosslinks with each other via Ca²⁺ bridges between their free carboxyl groups, rigidifying the cell wall and rendering it more able to withstand cell turgor, thus maintaining cell integrity. It also renders the cell wall more protective of penetrations by invading agents such as pathogens. Pathogens secrete cell wall degradative enzymes, in particular various pectinases, to degrade the host cell walls to gain penetrance. Oligogalacturonans (OGs), pectin fragmented to different DP, eg, between 10-15 (OG_DP10-15), are biologically active [99-103]. They function as elicitors to trigger host cell defense, such as turning on defense-related genes and closing stomata, pores on leaf surfaces for gaseous exchange, but are also used as entry points by pathogens. Biologically active OGs are inactivated by OG oxidases [98]. Cellular conditions such as various growth hormones could trigger cell wall modifications that could feedback regulate cellular activities needed for processes such as cell expansion, differentiation, and division [104,105]. Pectin methylesterase, de-esterified pectin, and OG have all been implicated as crucial for cell wall-related phenomena mediated by RALF-FER-LLG1 [69,97].

Pectin-FER Interaction Impacts Cell Wall Quality and Sensing

De-esterified pectin binds to both MALA and MALB from the FER extracellular domain (Figure 1A,B) [69,73,74,91]. The presence of FER is linked to the stable accumulation of de-esterified pectin on the cell surface, such as in the walls of specialized female reproductive tissues [85] (see Box 2). FER-pectin interaction mediates cell wall strength, which is important for cell growth and reproduction and protects it from stress-induced wall damage [40,91,105]. During vegetative growth, FER-pectin interaction is important for the morphogenesis of the jigsaw puzzle pattern of the leaf epidermis [40,73]. Cell elongation imposes stress on the cell wall, FER-pectin interaction maintains cell wall integrity during the growth hormone brassinosteroid-induced rapid growth phase [105]. When encountering stress, eg, high salinity, FER-pectin interaction prevents root cells from bursting and mediates resilience for survival [69,91]. Loss-of-FER resulted in fer mutant seedlings not being able to regain growth even when the stress conditions were mitigated. FER-pectin interaction is therefore important to maintain cell wall integrity, presumably by stabilizing de-esterified pectin associated with the wall matrix.

The FER-mediated and NO-executed polyspermy block in the ovules referred to earlier is also dependent on a FER-mediated, synergid cell-secreted, de-esterified pectin-enriched cell wall at the entrance to the female gametophyte (see Box 1 and Box 2) [85]. Growing pollen tubes secrete pectinases, producing pectic fragments that stimulate NO accumulation at the entrance to the female gametophyte, coincident with the arrival of the first pollen tube. Loss of FER diminished the pectin accumulation and rendered NO undetectable. Late-arriving pollen tubes continued to enter mutant ovules that had already received a pollen tube, giving rise to multiple pollen tubes gaining entries. This, together with pollen tubes failing to rupture due to the diminished ROS environment [49], gives rise to the dramatic pile-up of pollen tubes inside the female gametophyte that fer mutants are noted for (Box 1).

The NO-mediated blockade functions at least on two levels [85]. First, the FER- and de-esterified pectin-dependent NO accumulation at the entrance of the penetrated female gametophyte nitrosates LUREs and inactivates these secreted pollen tube attractants, and also prevents further LURE secretion, thus disengaging the mechanism that would guide more pollen tubes to an already penetrated ovule. Secondly, rupture of the already penetrated pollen tube generates an abrupt increase in [Ca²⁺] at the female gametophyte entrance. Though it remains to be directly demonstrated, the abrupt increase in [Ca²⁺] would induce extensive crosslinking between the de-esterified pectin, stiffening the cell wall matrix to ensure its non-penetrability by any late-arriving pollen tubes. Together, the FER to ROS plasma membrane to cytoplasmic signaling pathway and the cell wall-associated FER-pectin-NO pathway act to enable fertilization and avert polyspermy, respectively, thus ensuring maximum seed production and healthy progenies [18,42].

RALF1 Triggers FER- and LLG1-dependent Promiscuous Endocytosis

Ligand-receptor interaction typically triggers downstream signaling specifically mediated by the cognate receptor. This is generally followed by the endocytosis of the ligand-receptor complex to modulate intracellular signaling activities [106,107]. RALF1, however, induces not only FER and LLG1 endocytosis but also that of a battery of non-cognate targets in the plasma membrane in a FER- and LLG1-dependent manner [69]. Among these non-cognate targets are the cell growth-regulating H⁺-ATPase, several receptor kinases such as the receptor kinases BRI1 and FLS2 for the growth hormone brassinosteroid and bacterial elicitor flagellin 22, influx and efflux transporters PIN and AUX of the hormone auxin, respectively. Growth and the activity of H⁺-ATPases, brassinosteroid, auxin, and immunity signaling are intimately linked to FER-LLG1 functions [17,19,21]. RALF1 also augments uptake of the endocytic marker dye FM4-64, implying that the impact from signal activation of FER-LLG1 could be even more widespread. Loss of FER or LLG1 obliterates these RALF1-induced responses, revealing FER-LLG1 as a mediator of RALF1-induced promiscuous endocytosis. These results reflect that in response to signal activation, FER-LLG1 could simultaneously regulate the activity of numerous cellular pathways for diverse processes thus mediating a cell surface mechanism that enables its exceptionally broad functional range.

Pectin-RALF LLPS In Vitro

As a process that drives biomolecules to concentrate into condensates more readily able to overcome thresholds for their reactivities, the importance of LLPS in biological processes has long been recognized [108-112]. De-esterified pectin fragments are anionic (Box 2) and therefore should readily interact with cationic molecules in its milieu; pectin is known to undergo phase transition in the cell wall [113]. Besides being disordered rendering it prone for phase separation [114], RALFs are highly basic, eg, the pI of RALF1 is around 10.5, with 12 of its 49 amino acid residues being positively charged [69]. OG of various sizes, in particular OG_DP10-15 and OG_DP25-50, interact with several RALF peptides in vitro [69,95,96]. In the case of RALF1, when mixed with OG, they readily formed condensates with molecular dynamics and biochemical properties aligned with being products of LLPS (Figure 2C,D). FER extracellular domain and LLG1 are readily recruited to OG-RALF1, forming condensates of OG-RALF1-FER-LLG1 (Figure 2E,F).

A panel of RALF1 mutants altered specifically with eliminated key positively charged amino acid residues, cysteine and tyrosine residues speculated to contribute to LLPS, were tested for their efficacy in binding to OG. None devastated the capacity, but all produced significantly fewer and smaller peptide-OG condensates than those formed with wild-type RALF1. These observations, therefore, revealed parameters that contribute to OG-RALF1 interaction are consistent with those typical of disordered protein regions.

OG-RALF1 Phase Separation at the Cell Surface Mediates Receptor Recruitment and Endocytosis

Experiments using differentially labeled OG, RALF1, FER, and LLG1 established that the RALF1-triggered receptor clusters comprise all four of these components (Figure 2G). Similar to in vitro assembly of these receptor clusters (Figure 2E,F), both OG and RALF1 are required in RALF1-induced receptor clusters and endocytosis in vivo [69]. Fragmented pectin produced on the cell surface, typically de-esterified, or applied OGs are incorporated into the RALF1-triggered receptor clusters. Chemically or genetically reducing the level of de-esterified pectin inhibited these processes. RALF1-OG interaction also recruits other non-cognate targets, such as the immunity and brassinosteroid receptors FLS2 and BRI1, respectively, to co-cluster with FER, revealing a molecular basis of how RALF1 triggers the endocytosis of these non-cognate receptors. The RALF1 condensates are dynamic and sensitive to hexanediol, a diagnostic for LLPS due to its disruption of weak hydrophobic interaction resulting in condensate dissolution. Mutant RALF1s that displayed compromised capacity to interact with OG and in OG-RALF1 condensate formation in vitro also had reduced efficacy than wild-type RALF1 in inducing receptor endocytosis and inhibiting root growth. Together, these results are consistent with RALF1-triggered receptor clusters and endocytosis being mediated by LLPS.

Environmental Stress Triggers OG-RALF1 Phase Separation and Induces FER- and LLG1-Dependent Promiscuous Endocytosis as a Coping Mechanism

Succumbing to environmental stressors such as heat and drought devastates plant growth and productivity. Stressors like heat and drought attenuate plant growth, a coping response protecting plants from excessive growth-induced damage, so they are better able to emerge from growth arrest and regain growth when more favorable conditions return [115,116]. FER-LLG1 is important for plant survival from biotic and abiotic stressors and does so, at least partially, by mediating stress-induced promiscuous endocytosis [69]. It was determined that environmental stressors such as elevated temperature or high salinity stimulate mature RALF secretion and increase the production of fragmented pectin in the extracellular matrix. This is akin to applying RALF peptides exogenously or experimentally augmenting the level of de-esterified pectin to drive pectin-RALF-FER-LLG1 receptor clustering and endocytosis at the cell surface (see Supplementary Movie 1,2). Under stress, RALF1-OG phase separates and assembles into surface condensates, recruiting FER, LLG1, and other receptors, driving their clustering and elevating their overall endocytosis. Loss of FER, LLG1, or genetically reducing the plant capacity to secrete RALFs or produce de-esterified pectin were all inhibitory to heat- and salt-stress-induced promiscuous endocytosis. These mutant plants also lost their stress resilience and failed to emerge from growth arrest even when ambient conditions were restored. Therefore, the stress-induced, pectin-RALF-FER-LLG1-mediated cell surface response could attenuate numerous cell-surface regulator-regulated pathways, preventing irreversible damages, thus facilitating a coping mechanism that could recruit the participation of many signaling pathways for diverse processes.

FER-LLG1 as Anchors for Membrane Microdomain Assembly: A Global Signaling Strategy?

As discussed earlier, LLG1 binds FER and chaperones the receptor kinase to its functional location [40]. The GPI-AP-occupied sterol- and sphingolipid-enriched membrane subdomains [51-63] are known to be where signaling molecules, such as receptors, tend to concentrate and initiate their signaling activity. Segregation of sterols and sphingolipids from bulk-phase membrane lipids is a classic example of LLPS. RALF1-FER-LLG1 interaction induces numerous other cell surface regulators to coalesce with the FER-LLG1 coreceptor clusters could be triggered by the formation of micro/nano-domains nucleated by the peptide ligand binding to sterol- and sphingolipid-located LLG1. Among the plasma membrane- associated proteins that are endocytosed upon RALF1 treatment are REMORINs, proteins that have been shown biochemically to be associated with sterol- and sphingolipid membrane fractions and microscopically observed to reside in membrane micro/nanodomains [63]. Associated with the cytoplasmic surface of the plasma membrane, REMORINs have been proposed to serve as scaffolds for the assembly of other microdomain constituents. Therefore, while requiring further analyses, the assembly of OG-RALF-FER-LLG1 could be part of a broader mechanism that nucleates microdomains assembly.

Beginning from the ER, FER-LLG1 is a partnership of intriguing design. Lacking a cytoplasmic domain for signal dispatch, LLG1 nevertheless not only serves a critical role for FER functional capacitation but also could more broadly mark the membrane subdomains that it occupies for the assembly of other cell surface signaling molecules. The recruitment of many regulatory molecules for diverse processes into microdomain environments provides proximity to FER-LLG1. This might also underlie observations of FER cytoplasmic domain interacting with a large array of cytoplasmic molecules, some with key biological functions [30,38,115,116].

RALF1-FER-LLG1 Related Modules in Arabidopsis

The RALF1-FER-LLG1 related ligand-coreceptor modules in Arabidopsis studied thus far suggest the constituent proteins provide similar biochemical and molecular capacities to play different roles in the context of where they are expressed. For example, the leaf-abundant RALF23-FER-LLG1 plays an important role in regulating immunity responses to pathogens [26]. At least two other FER-related receptor kinases, LETUM1 and LETUM2, also anchor modules with important roles in disease signaling. LLG1 binds both LETUM1 and LETUM2 [117,118] to regulate a downstream MAPK cascade with the LETUM1/2-LLG1 complex serving as a scaffold for the assembly with additional components of the immunity signaling pathway. The male and female organs and cells have their designated constituents, such as the FER-LRE coreceptor assembled at the entrance of the female gametophyte for female fertility (Box 1) and the BUPS1/2-ANXUR1/2-LLG2/3-RALF4/19 modules in pollen [18,44,45,49]. Loss of any of the components of these pollen modules results in male sterility [44,45]. ANXURs and BUPSs form obligatory dimers; loss of function of both ANXURs, or loss of function in BUPSs induces male sterility. Several FER-related receptor kinases are also expressed in the stigma and ovules, and combinatorial mutations in these receptors induce subsets of fer phenotypes [46,75,119]. While initially recognized as pollen-specific, ANXURs are also expressed during vegetative growth in developmental stages vulnerable to diseases. ANXUR1 and ANXUR2 together play an important regulatory role in immunity signaling, linking cell surface pattern recognition receptors to intracellular receptors for pathogen effectors [120]. Moreover, mutational studies uncoupled ANXUR immunity and reproduction functions, revealing the evolution of distinct molecular interactions to serve different biological roles. These examples reflect not only how RALF-FER-LLG1 signaling can be broadly influential but also reveal intriguing designs that expand the biological roles of individual malectin-domain receptor kinases.

RALF1-FER-LLG1 Related Modules in Agriculturally Important Plant Species

Studies of FER signaling in Arabidopsis have led to efforts in achieving translationally important goals, such as overcoming interspecific reproduction barriers, which carries important implications for species diversification and increased productivity resulting from hybrid-rigor. Loss of FER, FER-related receptor kinases, stigma-expressed RALFs resulted in relaxing the pollination barriers for several distantly related interspecific species, allowing penetration of the pollen tubes [48,75]. Moreover, in the vegetable crop Brassica rapa, genetically down-regulating the stigmatic RALF-FER-LLG1-controlled ROS production pathway rendered its stigma more readily penetrable by pollen from distant species, resulting in hybrid embryo formation [48]. This opens the door to generating hybrids from species with various desirable traits, such as pathogen resistance, into the cultivated Brassica species.

To-date, FER-related signaling modules have been implicated in a broad range of agricultural species, revealing potential roles in mediating resistance to pathogens and environment stresses in major staple crops like maize and rice to vegetable, fruit and industrially important crops such as tomato, apples, and cotton [121-130]. RALF homologs have also been identified in animal and microbial disease-causing agents, such as nematodes and Fusarium [131-134]. As more advances are uncovered in how the RAFL-FER-LLG1 signaling module contributes to the performance of agricultural species, the knowledge should contribute to rational designs to improve crop yields, ascertaining production and food security to meet global nutritional needs.