FERONIA: A Receptor Kinase at the Core of a Global Signaling Network

Abstract

Initially identified as a key regulator of female fertility in Arabidopsis, the FERONIA (FER) receptor kinase is now recognized as crucial for almost all aspects of plant growth and survival. FER partners with a glycosylphosphatidylinositol-anchored protein of the LLG family to act as coreceptors on the cell surface. The FER-LLG coreceptor interacts with different RAPID ALKALINIZATION FACTOR (RALF) peptide ligands to function in various growth and developmental processes and to respond to challenges from the environment. The RALF-FER-LLG signaling modules interact with molecules in the cell wall, cell membrane, cytoplasm, and nucleus and mediate an interwoven signaling network. Multiple FER-LLG modules, each anchored by FER or a FER-related receptor kinase, have been studied, illustrating the functional diversity and the mechanistic complexity of the FER family signaling modules. The challenges going forward are to distill from this complexity the unifying schemes where possible and attain precision and refinement in the knowledge of critical details upon which future investigations can be built. By focusing on the extensively characterized FER, this review provides foundational information to guide the next phase of research on FER in model as well as crop species and potential applications for improving plant growth and resilience.

Keywords: GPI-AP; RAC/ROP; RALF; RAPID ALKALINIZATION FACTOR; ROS; cytoplasmic pathway; extracellular matrix; glycosylphosphatidylinositol-anchored protein; growth; nuclear pathway; reproduction; survival.

Figure 1

The multitasking FER. Loss of FER in Arabidopsis induces a plethora of growth and reproduction phenotypes. An abbreviated collection of these phenotypes is shown here. (a–e) Reproduction phenotypes (22, 24, 59, 108). (a) A diagram of PT–Ov interaction. PTs target Ovs to penetrate the FG, each transporting two Sp cells in its cytoplasm. The CC is the precursor to the seed endosperm. SCs produce attractants, and the first-arriving PT enters one of the SCs; late-approaching PTs are deterred and instead enter other not-yet-penetrated Ovs. The FA is a thickened cell wall region secreted by the synergids. In and Ou are precursors of the seed coat. M is the ovular aperture targeted by the pollen tube. (b) PT growth in WT or fer pistils. In WT pistils, a single PT exits from the main growth path in the TT to target Ovs one at a time, and each bursts to release sperm upon penetrating the FG. In fer pistils, the one PT:one Ov pattern is perturbed, and bundles of 2 to 3 PTs exit from the TT. Multiple PTs penetrate a single fer Ov but fail to burst, resulting in the PT pileup phenotype. (c) Individual Ovs showing a single burst PT in a WT Ov and a pileup of unburst PTs in fer Ovs. (d, top) A WT Ov stained for de-esterified pectin and (bottom) a WT Ov stained for NO and the SCs are filled with the cytoplasm from a just-penetrated and -burst Tomato-labeled PT. (e) Siliques from reciprocal crosses show a (left) WT pistil pollinated by fer pollen with a full seed set, but (right) seed yield is reduced in a fer pistil pollinated by WT pollen. (f–l) Growth defects and stress sensitivity of fer seedlings (23, 31, 74). (f) Growth phenotypes. (Top) The most severe seedling defect is growth arrest; (bottom) when not arrested, growth to maturity is consistently delayed. (g, top) Etiolated WT seedlings grown in the dark; (bottom) fer seedlings de-etiolate in the dark and are compromised in gravitropism. (h) fer leaf epidermal pavement cells lack the jigsaw puzzle shape characteristic of WT pavement cells. Auxin and RAC/ROP signaling are both required for the pavement cell shape differentiation (29, 98, 99). (i) fer trichomes are deformed. (j) fer root hairs burst, and cytoplasm is often seen leaking out of the root hair cells. Mutant roots lack ROS, a result of suppressed RAC/ROP-controlled, NADPH oxidase–dependent ROS production. The RAC/ROP-to-ROS pathway is crucial for polarized cell growth (29, 33, 98, 99). fer roots are not responsive to auxin-stimulated ROS increase and auxin-stimulated root hair development (23). (k) Under high-salt conditions, root cells of fer seedlings burst (A. Cheung, unpublished observations) and root growth is arrested (31). (l) Germinating fer seedlings are hypersensitive to ABA and fail to turn green. llg1 mutants phenocopy fer seedlings; lre mutants phenocopy fer reproduction phenotype (74). Abbreviations: A, antipodal cells; ABA, abscisic acid; CC, central cell; EC, egg cell; FA, filiform apparatus; FER, FERONIA; FG, female gametophyte; In, inner integument; M, micropyle; Ou, outer integument; Ov, ovule; PT, pollen tube; ROS, reactive oxygen species; SC, synergid cell; Sp, sperm; TT, transmitting track; VN, vegetative cell nucleus of the pollen tube; WT, wild-type. Panels a and e adapted from Reference , panels b–d adapted from Reference , and panels f–j and l adapted from Reference .

Figure 2

Core components of the FER signaling module. (a) Domain map of FER, representative of the FER family receptor kinases. Tandem Malectin-like domains are designated MALA and MALB. Alleles referred to in the text are indicated. Gly41Ser in fer-ts (67) is analogous to Gly37Asp and Glu150Lys conversion in MALA and MALB, respectively, in the1-1 and the1-2 mutations in THESEUS1 (54). The ROPGEF-interacting domain spans the C-terminal half of the FER cytoplasmic domain (23). fer-8 is defective in the FER-to-ROS pathway (126). LLG1 binds the exJM (74). (b) Three-dimensional structures of the ANX1^ECD, ANX2^ECD, and FERecd show similar architecture. (c) The ECD of apo-FER and of the RALF23-LLG2-FERecd heterocomplex. (d) A model of the FER-RAC/ROP-ROS signaling pathway. LLG is postulated to chaperone and deliver LLG-bound FER from the ER to the functional location for the FER-LLG coreceptor pair, presumably in the LLG-destined membrane microdomain. Unbound FER is transported through the default secretory pathway to the cell membrane, where it remains inactive. Signals trigger ligand-activated FER to the RAC/ROP GTPase pathway, which impacts diverse cytoplasmic response pathways. (e) Selected Arabidopsis RALF peptides and their amino acid sequence and functional features. A subset of RALFs are expressed as prepro-peptides with a predictive cleavage site for S1P (1, 145). The top panel shows not-yet-processed RALF1, a prototypical RALF peptide (1). Most RALF peptides have four Cys residues; others have two as indicated (1). Abbreviations: ANX, ANXUR; ATP, adenosine triphosphate; ECD, extracellular domain; ER, endoplasmic reticulum; exJM, extracellular juxtamembrane region; FER, FERONIA; FERecd, FERONIA extracellular domain; GDP, guanosine diphosphate; GTP, guanosine triphosphate; K, kinase; LLG, LORELEI-like glycosylphosphatidylinositol-anchored protein; MALA, Malectin-like A; MALB, Malectin-like B; RALF, RAPID ALKALINIZATION FACTOR; ROPGEF, ROP-guanine nucleotide exchange factor; ROS, reactive oxygen species; S1P, SITE-1 PROTEASE; srn, sirène; SS, signal peptide; TM, transmembrane. Panels a and d adapted from Reference , panels b and c adapted from Reference , and panel e includes data from References and .

Figure 3

The core FER signaling pathway and its elaborators along the cell surface. The FER-LLG1–ROPGEF–RAC/ROP signaling pathway is considered the core of the broader FER-LLG1 signaling network. Elaborators from the extracellular matrix, or the apoplast, to the cytoplasm and nucleus discussed in the text (see Sections 4 and 5) are depicted. RLKs (left) collectively refer to FLS2, BRI1 (129), and potentially additional receptor kinases, such as stigma-located SRK (right), whose interaction with FER, also a receptor kinase, is regulated in trans by pollen S-factor SCR/SP11 and impacts the FER-to-ROS pathway (57). NADPH oxidase, which produces ROS, is one of several RAC/ROP effectors and has been demonstrated to mediate several FER-controlled processes. ABI2 integrates into the FER core pathway via its interaction with RAC/ROPs (152). H⁺-ATPase is central to RALF-regulated growth (4, 103). The schematics for H⁺-ATPase are intended to demonstrate that (i) RALF-induced inhibition of H⁺-efflux induces medium alkalinization, and this aligns with the growth inhibitory activity of RALFs (4, 103), and (ii) RALF1 triggers the phosphorylation of AHA2 (52). Molecular and biochemical interactions providing causal linkages for the RALF-signaled H⁺-ATPase phosphorylation remain to be established. Dashed arrows indicate translocation. Abbreviations: ABI, Abscisic acid–insensitive; AHA2, Arabidopsis H⁺-ATPase 2; BRI1, Brassinosteroid Insensitive 1; ECD, extracellular domain; FER, FERONIA; FLS2, Flagellin-Sensing 2; K, kinase; LLG, LORELEI-like glycosylphosphatidylinositol-anchored protein; LRX, leucine-rich repeat extensin-like; MLO, Powdery Mildew Resistance Locus O; MYC, a bHLH (basic helix-loop-helix) transcription factor; PCP, Pollen Coat Protein; RALF, RAPID ALKALINIZATION FACTOR; RLCK, receptor-like cytoplasmic kinase; RLK, receptor-like kinase; ROPGEF, ROP-guanine nucleotide exchange factor; ROS, reactive oxygen species; SCR/SP11, S-Locus Cysteine-Rich/S-Locus Protein 11; SRK, S-Locus Receptor Kinase; TOR, TARGET OF RAPAMYCIN.