TOO MANY MOUTHS (TMM; RLP17) is a plasma-membrane leucine-rich-repeat receptor-like protein (RLP) with an extracellular LRR domain and a single transmembrane segment but no cytoplasmic kinase domain. It is expressed in proliferating stomatal-lineage (postprotodermal) cells and functions as a co-receptor for the ERECTA-family receptor kinases (ERECTA, ERL1, ERL2). TMM forms constitutive heteromeric complexes with ERECTA and ERL1 (and associates with SERK co-receptor kinases), and the TMM-ERf complex creates the binding pocket that recognizes the inhibitory EPF1 and EPF2 peptides and the competing positive peptide stomagen/EPFL9, while excluding the stem-growth EPFL4/EPFL6 peptides. TMM therefore acts as a specificity switch that directs ERECTA-family signalling, via the YODA-MKK4/5-MPK3/6 cascade, toward inhibition of stomatal development and the orientation of spacing divisions. Loss of TMM randomizes the orientation of asymmetric spacing divisions and permits entry divisions next to existing stomata, producing stomatal clusters in leaves, whereas stomata are absent from some organs such as inflorescence stems, reflecting region-specific positive and negative effects mediated through different EPF/EPFL ligands.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:19452453 Proteomic profiling of tandem affinity purified 14-3-3 prote... | REMOVE | Summary: Generic protein binding from a 14-3-3 (GRF2/AT1G78300) tandem-affinity-purification proteomics study. Reason: Generic protein binding is uninformative. The interaction derives from a high-throughput 14-3-3 complex profiling study and has no established functional relevance for TMM, which has no cytoplasmic domain of substance; removal does not imply the reported co-purification is false. |
| GO:0005515 protein binding | IPI PMID:26083750 Competitive binding of antagonistic peptides fine-tunes stom... | MODIFY | Summary: TMM binds the stomagen/EPFL9 peptide (Q9SV72). Reason: The interaction is direct binding of a secreted peptide ligand to the TMM ectodomain; peptide binding is the informative term (and is also annotated separately from the same paper). Proposed replacements: peptide binding Supporting Evidence: PMID:26083750 Both EPF2 and Stomagen directly bind to ER and its co-receptor TOO MANY MOUTHS. |
| GO:0005886 plasma membrane | EXP PMID:22241782 Direct interaction of ligand-receptor pairs specifying stoma... | ACCEPT | Summary: Functional epitope-tagged TMM detected in membrane (microsomal) fractions. Reason: TMM is a single-pass transmembrane RLP that associates with ERECTA-family receptors and binds apoplastic peptides; plasma membrane localization is well supported. Supporting Evidence: PMID:22241782 The epitope-tagged TMM, ERECTA, and ERL1 were detected in membrane (microsomal) fractions, consistent with their predicted subcellular localizations |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of plasma membrane localization for LRR RLPs. Reason: Consistent with TMM structure and its function as a cell-surface co-receptor. Supporting Evidence: PMID:12040198 TMM encodes a leucine-rich repeat-containing receptor-like protein expressed in proliferative postprotodermal cells. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to plasma membrane. Reason: Correct for a cell-surface LRR receptor-like protein. |
| GO:0005886 plasma membrane | NAS PMID:12040198 Control of stomatal distribution on the Arabidopsis leaf sur... | ACCEPT | Summary: Plasma membrane localization stated on the basis of TMM's predicted receptor-like protein structure. Reason: Supported by later biochemical data (membrane fractions, association with ERECTA-family receptors). Supporting Evidence: PMID:12040198 TMM encodes a leucine-rich repeat-containing receptor-like protein expressed in proliferative postprotodermal cells. |
| GO:0007165 signal transduction | IC PMID:11751054 The leucine-rich repeat as a protein recognition motif. | ACCEPT | Summary: Curator inference of signal transduction from LRR protein-recognition function. Reason: TMM is a co-receptor that shapes ERECTA-family signalling in response to EPF peptides; involvement in signal transduction is correct though general. The specific output is captured by stomatal complex patterning. Supporting Evidence: PMID:22241782 TMM modulates the signal transduction via association with the ERECTA family |
| GO:0008356 asymmetric cell division | IMP PMID:11090210 Oriented asymmetric divisions that generate the stomatal spa... | KEEP AS NON CORE | Summary: tmm randomizes the orientation of asymmetric spacing divisions. Reason: TMM signalling orients, and restricts the location of, asymmetric divisions in stomatal-lineage cells; the protein does not execute the division but regulates its placement. Retained as a valid but non-core process; the core process is stomatal complex patterning. Supporting Evidence: PMID:11090210 the orientation of asymmetric divisions that pattern stomata, and the control of which cells will enter the stomatal pathway. |
| GO:0008356 asymmetric cell division | IMP PMID:9684356 Divergent regulation of stomatal initiation and patterning i... | KEEP AS NON CORE | Summary: tmm affects asymmetric (stomatal initiation) divisions in a region-specific way. Reason: As above; regulatory involvement in asymmetric entry/spacing divisions, non-core relative to stomatal patterning. Supporting Evidence: PMID:9684356 This suggests that TMM represents an unusual type of gene regulating plant cell development in that it can either influence stomatal initiation in a positive or negative fashion depending on region. |
| GO:0009737 response to abscisic acid | IMP PMID:18434605 A genome-wide functional investigation into the roles of rec... | KEEP AS NON CORE | Summary: tmm-1 and Atrlp17-1 show decreased ABA sensitivity in a genome-wide RLP mutant screen. Reason: A secondary phenotype from a large-scale screen; no mechanism links TMM to ABA perception, and the effect may be indirect (e.g. via altered epidermal/stomatal development). Kept as non-core. Supporting Evidence: PMID:18434605 In addition to the previously described stomatal clustering phenotype, tmm-1 and Atrlp17-1 that both carry a mutation in the AtRLP gene TMM displayed decreased sensitivity to ABA. |
| GO:0010090 trichome morphogenesis | IMP PMID:24553751 New phenotypic characteristics of three tmm alleles in Arabi... | KEEP AS NON CORE | Summary: TMM overexpression reduced leaf trichome number and branching. Reason: Based on an overexpression phenotype reported in an abstract-only paper; plausibly an indirect effect of altered epidermal patterning. Retained as non-core pending mechanistic support. Supporting Evidence: PMID:24553751 Interestingly, overexpression of TMM resulted in the reduction of leaf trichomes and their branches, and this might reveal a new function of TMM in trichome development. |
| GO:0010375 stomatal complex patterning | IMP PMID:11090210 Oriented asymmetric divisions that generate the stomatal spa... | ACCEPT | Summary: tmm mutants violate the one-cell spacing rule, producing stomatal clusters. Reason: Core biological role. TMM-containing receptor complexes perceive EPF signals that orient spacing divisions and prevent stomata from forming in contact. Supporting Evidence: PMID:11090210 tmm randomizes this orientation and releases a prohibition on asymmetric division in cells at specific locations, resulting in stomatal clusters. |
| GO:0010375 stomatal complex patterning | IMP PMID:11536724 The too many mouths and four lips mutations affect stomatal ... | ACCEPT | Summary: Original isolation of tmm with clustered stomata. Reason: Founding genetic evidence for TMM's role in stomatal patterning/production. Supporting Evidence: PMID:11536724 The tmm mutation results in stomatal clustering and increased precursor cell formation in cotyledons and a virtual absence of stomata in the inflorescence stem. |
| GO:0010375 stomatal complex patterning | IMP PMID:9684356 Divergent regulation of stomatal initiation and patterning i... | ACCEPT | Summary: Organ-specific quantification of stomatal clustering in tmm. Reason: Supports the core patterning role. Supporting Evidence: PMID:9684356 This patterning is violated in the too many mouths (tmm) and four lips (flp) mutations |
| GO:0010376 stomatal complex formation | IMP PMID:11090210 Oriented asymmetric divisions that generate the stomatal spa... | ACCEPT | Summary: tmm alters whether cells enter the stomatal pathway (stomatal formation). Reason: TMM controls which cells enter the stomatal pathway and, in some organs (e.g. stems), is required for stomata to form at all; an accurate description of its regulatory role in stomatal formation. Supporting Evidence: PMID:11090210 the control of which cells will enter the stomatal pathway |
| GO:0010376 stomatal complex formation | IMP PMID:9684356 Divergent regulation of stomatal initiation and patterning i... | ACCEPT | Summary: tmm lacks stomata in some regions and has excess in others. Reason: Region-specific positive and negative effects of TMM on stomatal initiation; consistent with TMM acting as a ligand-specificity switch for ERECTA-family receptors. Supporting Evidence: PMID:9684356 The tmm mutation has a more complex region-specific phenotype in that some regions lack stomata entirely, other regions have excess stomata |
| GO:0016020 membrane | IDA PMID:22241782 Direct interaction of ligand-receptor pairs specifying stoma... | ACCEPT | Summary: TMM detected in microsomal membrane fractions. Reason: Correct; the more specific plasma membrane term is also annotated. Supporting Evidence: PMID:22241782 The epitope-tagged TMM, ERECTA, and ERL1 were detected in membrane (microsomal) fractions |
| GO:0016020 membrane | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA prediction of membrane localization. Reason: Correct, though less specific than plasma membrane. |
| GO:0016020 membrane | TAS PMID:12068095 Prediction of glycosylphosphatidylinositol-anchored proteins... | ACCEPT | Summary: Membrane localization stated in a genome-wide GPI-anchored protein prediction study. Reason: TMM is membrane-associated (it has a transmembrane segment); the membrane term is correct regardless of whether a GPI anchor is used, and the more specific plasma membrane term is annotated. |
| GO:0016020 membrane | TAS PMID:12805588 Identification of glycosylphosphatidylinositol-anchored prot... | ACCEPT | Summary: Membrane localization stated in a proteomic GPI-anchored protein identification study. Reason: As above; membrane localization is correct. |
| GO:0033612 receptor serine/threonine kinase binding | IPI PMID:26320950 Differential Function of Arabidopsis SERK Family Receptor-li... | ACCEPT | Summary: TMM associates with SERK-family co-receptor kinases (SERK1, SERK2, BAK1/SERK3, SERK4) in a ligand-independent manner. Reason: Informative binding term describing TMM's role as a non-catalytic subunit of a stomatal receptor complex ('receptorsome') containing ERECTA-family and SERK receptor kinases. Supporting Evidence: PMID:26320950 SERKs associate with the receptor-like protein (RLP) TMM, a signal modulator of stomata development, in a ligand-independent manner, suggesting that ERECTA, SERKs, and TMM form a multiprotein receptorsome |
| GO:0033612 receptor serine/threonine kinase binding | IPI PMID:26320950 Differential Function of Arabidopsis SERK Family Receptor-li... | ACCEPT | Summary: TMM associates with SERK-family co-receptor kinases (SERK1, SERK2, BAK1/SERK3, SERK4) in a ligand-independent manner. Reason: Informative binding term describing TMM's role as a non-catalytic subunit of a stomatal receptor complex ('receptorsome') containing ERECTA-family and SERK receptor kinases. Supporting Evidence: PMID:26320950 SERKs associate with the receptor-like protein (RLP) TMM, a signal modulator of stomata development, in a ligand-independent manner, suggesting that ERECTA, SERKs, and TMM form a multiprotein receptorsome |
| GO:0033612 receptor serine/threonine kinase binding | IPI PMID:26320950 Differential Function of Arabidopsis SERK Family Receptor-li... | ACCEPT | Summary: TMM associates with SERK-family co-receptor kinases (SERK1, SERK2, BAK1/SERK3, SERK4) in a ligand-independent manner. Reason: Informative binding term describing TMM's role as a non-catalytic subunit of a stomatal receptor complex ('receptorsome') containing ERECTA-family and SERK receptor kinases. Supporting Evidence: PMID:26320950 SERKs associate with the receptor-like protein (RLP) TMM, a signal modulator of stomata development, in a ligand-independent manner, suggesting that ERECTA, SERKs, and TMM form a multiprotein receptorsome |
| GO:0033612 receptor serine/threonine kinase binding | IPI PMID:26320950 Differential Function of Arabidopsis SERK Family Receptor-li... | ACCEPT | Summary: TMM associates with SERK-family co-receptor kinases (SERK1, SERK2, BAK1/SERK3, SERK4) in a ligand-independent manner. Reason: Informative binding term describing TMM's role as a non-catalytic subunit of a stomatal receptor complex ('receptorsome') containing ERECTA-family and SERK receptor kinases. Supporting Evidence: PMID:26320950 SERKs associate with the receptor-like protein (RLP) TMM, a signal modulator of stomata development, in a ligand-independent manner, suggesting that ERECTA, SERKs, and TMM form a multiprotein receptorsome |
| GO:0033612 receptor serine/threonine kinase binding | IPI PMID:28536146 A receptor-like protein acts as a specificity switch for the... | ACCEPT | Summary: TMM forms constitutive complexes with ERECTA and ERL1 (structural and biochemical study). Reason: Direct interaction with the ERECTA-family receptor kinases is the mechanistic basis of TMM's co-receptor function. Supporting Evidence: PMID:28536146 Here we show that TMM and ER or ER-LIKE1 (ERL1) form constitutive complexes, which recognize EPF1 and EPF2, but the single ERfs do not. |
| GO:0033612 receptor serine/threonine kinase binding | IPI PMID:28536146 A receptor-like protein acts as a specificity switch for the... | ACCEPT | Summary: TMM forms constitutive complexes with ERECTA and ERL1 (structural and biochemical study). Reason: Direct interaction with the ERECTA-family receptor kinases is the mechanistic basis of TMM's co-receptor function. Supporting Evidence: PMID:28536146 Here we show that TMM and ER or ER-LIKE1 (ERL1) form constitutive complexes, which recognize EPF1 and EPF2, but the single ERfs do not. |
| GO:0038023 signaling receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of signaling receptor activity for the LRR RLP node. Reason: Correct at this general level. TMM lacks an intracellular signalling domain and acts as a co-receptor that, together with an ERECTA-family kinase, forms the binding site for EPF1/EPF2; the more specific coreceptor activity (a child of signaling receptor activity) is used in core functions. Supporting Evidence: PMID:28536146 TMM interaction with ERL1 creates a binding pocket for recognition of EPF1 and EPF2, indicating that the constitutive TMM-ERf complexes function as the receptors of EPF1 and EPF2. |
| GO:0042277 peptide binding | IPI PMID:26083750 Competitive binding of antagonistic peptides fine-tunes stom... | ACCEPT | Summary: TMM binds the stomagen (EPFL9) peptide. Reason: Direct binding of EPF-family peptides (stomagen and EPF2) to TMM is documented; peptide binding reflects its ligand-recognition role as a co-receptor. Supporting Evidence: PMID:26083750 Both EPF2 and Stomagen directly bind to ER and its co-receptor TOO MANY MOUTHS. |
| GO:0050832 defense response to fungus | IMP PMID:27446127 ERECTA and BAK1 Receptor Like Kinases Interact to Regulate I... | KEEP AS NON CORE | Summary: tmm mutants show altered resistance to the necrotrophic fungus Plectosphaerella cucumerina. Reason: TMM contributes with ERECTA-family receptors to resistance to this fungus; genuine but a secondary role relative to stomatal development. Supporting Evidence: PMID:27446127 Here, we report that the developmental-associated ER partners, ERL1 and ERL2 and TMM, play overlapping functions in Arabidopsis defense responses against PcBMM |
| GO:0071215 cellular response to abscisic acid stimulus | IMP PMID:18434605 A genome-wide functional investigation into the roles of rec... | KEEP AS NON CORE | Summary: Reduced ABA sensitivity of tmm mutants. Reason: Secondary phenotype from a genome-wide RLP mutant screen; not a core function. Supporting Evidence: PMID:18434605 In addition to the previously described stomatal clustering phenotype, tmm-1 and Atrlp17-1 that both carry a mutation in the AtRLP gene TMM displayed decreased sensitivity to ABA. |
| GO:0071215 cellular response to abscisic acid stimulus | IMP PMID:24553751 New phenotypic characteristics of three tmm alleles in Arabi... | KEEP AS NON CORE | Summary: Altered ABA responses of new tmm alleles in germination and seedling growth. Reason: Allele-dependent ABA phenotypes reported in an abstract-only paper; mechanism unknown, likely indirect. Supporting Evidence: PMID:24553751 tmm-5 and tmm-6 were hypersensitive to abscisic acid (ABA) in seedling growth and seed germination |
| GO:1905034 regulation of antifungal innate immune response | IMP PMID:27446127 ERECTA and BAK1 Receptor Like Kinases Interact to Regulate I... | KEEP AS NON CORE | Summary: TMM genetically regulates antifungal immune responses together with ERECTA. Reason: As for defense response to fungus; secondary role. Supporting Evidence: PMID:27446127 Genetic analyses demonstrated that ER acts in a combinatorial specific manner with ERL1, ERL2, and TMM to control PcBMM resistance. |
| GO:0015026 coreceptor activity | IDA PMID:28536146 A receptor-like protein acts as a specificity switch for the... | NEW | Summary: TMM acts as a co-receptor with ERECTA-family receptor kinases; the TMM-ERL1/ER complex, not the kinase alone, forms the EPF1/EPF2 binding pocket. Reason: Direct biochemical and structural evidence that TMM, which lacks a kinase domain, cooperates with a nearby primary receptor kinase to bind the peptide ligand and initiate signalling, matching the definition of coreceptor activity and more informative than the IBA signaling receptor activity. Supporting Evidence: PMID:28536146 TMM interaction with ERL1 creates a binding pocket for recognition of EPF1 and EPF2, indicating that the constitutive TMM-ERf complexes function as the receptors of EPF1 and EPF2. PMID:26083750 Both EPF2 and Stomagen directly bind to ER and its co-receptor TOO MANY MOUTHS. |
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Download this section (compressed HTML)Q: How does a single co-receptor produce opposite, organ-specific effects on stomatal initiation (clusters in leaves, no stomata in stems), and is this fully explained by TMM's exclusion of EPFL4/EPFL6 from ERECTA-family receptors?
Q: Is TMM localization or abundance itself regulated during stomatal lineage progression (e.g. by SPCH-dependent transcription or endocytosis), providing feedback on EPF sensitivity?
Experiment: Structure-guided TMM interface mutants that abolish ERf binding but preserve folding, tested for complementation of tmm leaf clustering and stem stomatal absence, to separate ligand-pocket formation from EPFL4/6 exclusion in vivo.
Type: structure-function genetics
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