CLV3 (CLAVATA3) is a secreted signaling peptide of the CLV3/ESR (CLE) family that controls stem-cell homeostasis in the shoot apical and floral meristems of Arabidopsis. It is synthesized as a 96-residue precursor with an N-terminal signal peptide and is proteolytically processed and post-translationally modified into a short (12-13 amino acid) arabinosylated glycopeptide (MCLV3 / CLV3p) derived from the conserved C-terminal CLE motif. The mature peptide carries hydroxyprolines at Pro-73 and Pro-76 and an O-linked arabinose chain on hydroxyproline Pro-76 that enhances receptor-binding affinity, with His-81 essential for activity. CLV3 is expressed specifically in the stem cells of the central zone at the meristem apex, is secreted into the extracellular space (apoplast), and acts cell-non-autonomously as a ligand. It binds the extracellular leucine-rich-repeat domains of the receptor serine/threonine kinases CLV1, BAM1 and BAM2 with nanomolar affinities. It also signals through the receptor-like protein CLV2, which lacks a kinase domain and acts with the pseudokinase CRN/CORYNE; radioligand assays reported direct CLV3 binding by CLV2, but photoaffinity labelling did not detect it, so CLV2 may act as a co-receptor rather than a direct binding receptor. Receptor activation triggers a signal transduction cascade that represses the homeodomain transcription factor WUSCHEL (WUS) in the underlying organizing center, establishing a CLV3-WUS negative feedback loop that balances stem-cell proliferation against differentiation. Loss of CLV3 function enlarges shoot and floral meristems and increases organ number, whereas elevated CLV3 signaling consumes the meristem and drives premature differentiation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: CLV3 is a secreted protein; localization to the extracellular region is correct and is a core aspect of its function as an apoplastic ligand. This IEA annotation (from UniProt subcellular location mapping) is strongly supported by direct experimental evidence for apoplastic localization. Reason: Extracellular localization is fundamental to CLV3 function as a secreted cell-non-autonomous ligand and is experimentally demonstrated. GO:0048046 apoplast (IDA) is a more specific child term that is also retained. Supporting Evidence: PMID:12034890 export to the extracellular space is required for its function in activating the CLV1/CLV2 receptor complex |
| GO:0033612 receptor serine/threonine kinase binding | IEA GO_REF:0000002 | ACCEPT | Summary: This InterPro2GO-derived (IEA) annotation assigns the CLV3/ESR family the molecular function of binding receptor serine/threonine kinases. This is the most informative molecular function for CLV3 and is independently confirmed by experimental IPI annotations showing the mature CLV3 peptide binds the LRR receptor kinases CLV1, BAM1 and BAM2. Reason: The mature CLV3 (MCLV3/CLV3p) peptide is the ligand for the LRR receptor serine/threonine kinases CLV1/BAM1/BAM2; receptor kinase binding is the core molecular function and is experimentally supported. Supporting Evidence: PMID:20626648 CLV2, CLV1 and the CLV1 homologs BAM1 and BAM2 all bind to the CLV3-derived CLE peptide with similar kinetics file:ARATH/CLV3/CLV3-deep-research-falcon.md derived from the C-terminal CLE motif of the precursor and recognized by LRR receptor complexes at the plasma membrane |
| GO:0045168 cell-cell signaling involved in cell fate commitment | IDA PMID:16603652 Dynamic and compensatory responses of Arabidopsis shoot and ... | ACCEPT | Summary: CLV3 is secreted from stem cells in the central zone and signals at short range to the underlying organizing center to repress WUS, controlling whether cells remain as stem cells or differentiate. This is an accurate and core description of CLV3 function as an intercellular signal directing cell fate. Reason: Cell-non-autonomous, short-range signaling that commits meristem cells to stem-cell versus differentiated fate is a defining biological process for CLV3, directly demonstrated by inducible-expression experiments. Supporting Evidence: PMID:16603652 Stem cells express the secreted peptide CLV3 that activates a signal transduction cascade to restrict WUS expression file:ARATH/CLV3/CLV3-deep-research-falcon.md maintaining stem cell homeostasis in the shoot (and floral) apical meristem |
| GO:0007166 cell surface receptor signaling pathway | IDA PMID:16603652 Dynamic and compensatory responses of Arabidopsis shoot and ... | ACCEPT | Summary: CLV3 acts as the extracellular ligand that activates cell-surface LRR receptor kinases (CLV1/BAM/CLV2-CRN) on the plasma membrane of organizing-center cells, initiating an intracellular signal transduction cascade. This is a correct and core process annotation for CLV3. Reason: CLV3 initiates a bona fide cell-surface receptor signaling pathway by binding plasma-membrane LRR receptor kinases; this is central to its mechanism of action. Supporting Evidence: PMID:16603652 Stem cells express the secreted peptide CLV3 that activates a signal transduction cascade to restrict WUS expression |
| GO:0005102 signaling receptor binding | IPI PMID:10915624 Dependence of stem cell fate in Arabidopsis on a feedback lo... | KEEP AS NON CORE | Summary: This IPI annotation (WITH CLV1 and CLV2 AGI loci) captures that CLV3 acts through binding the CLV1/CLV2 signaling receptors. The term is correct but is a more general parent of receptor serine/threonine kinase binding (GO:0033612). It remains the appropriate term for CLV3 association with CLV2, which is a receptor-like protein lacking a kinase domain; direct CLV3 binding by CLV2 is disputed (PMID:25754504 detected none by photoaffinity labelling). Reason: Correct but less specific than GO:0033612; useful because it also covers binding to the non-kinase receptor-like protein CLV2. The more informative receptor serine/threonine kinase binding term is treated as the core molecular function. Supporting Evidence: PMID:10915624 CLV3 signaling occurs exclusively through a CLV1/CLV2 receptor kinase complex PMID:20626648 CLV3 CLE-binding sites within membrane fractions were generated by expression of full-length CLV2 |
| GO:0002221 pattern recognition receptor signaling pathway | IEP NOT PMID:22923673 The shoot apical meristem regulatory peptide CLV3 does not a... | ACCEPT | Summary: This is a NOT (negated) annotation recording that CLV3 does not act through a pattern recognition receptor (FLS2) signaling pathway. It directly counters the earlier claim (PMID:21499263) that CLV3p triggers FLS2-mediated immunity. Segonzac et al. could not reproduce CLV3p recognition by FLS2 and showed SAM immunity is independent of CLV3 perception. The negation should be retained. Reason: The negated annotation correctly documents that CLV3 does not function through PRR/FLS2 signaling, reflecting the current consensus that the proposed CLV3p-FLS2 immunity is not reproducible. Supporting Evidence: PMID:22923673 FLS2 does not recognize CLV3 and that the shoot apical meristem is immune to bacteria independently of CLV3 perception |
| GO:0005576 extracellular region | ISM GO_REF:0000122 | ACCEPT | Summary: A second (ISM, AtSubP-predicted) annotation to the extracellular region. The localization is correct and experimentally supported, consistent with CLV3 being a secreted apoplastic peptide. Reason: Extracellular localization is correct and core; duplicates the UniProt-derived extracellular region annotation and is backed by experimental apoplast evidence. Supporting Evidence: PMID:12034890 export to the extracellular space is required for its function in activating the CLV1/CLV2 receptor complex |
| GO:0005739 mitochondrion | ISM GO_REF:0000122 | REMOVE | Summary: This mitochondrial localization is an electronic prediction (ISM, AtSubP tool, GO_REF:0000122) that is biologically implausible. CLV3 has an N-terminal secretory signal peptide (residues 1-21), is processed into a secreted CLE peptide, and is experimentally localized to the apoplast/extracellular space. There is no evidence for a mitochondrial pool, and the signal-peptide-driven secretory route is incompatible with mitochondrial targeting. Reason: Demonstrably wrong algorithmic subcellular-location prediction. CLV3 is a signal-peptide-bearing secreted peptide localized to the extracellular space; mitochondrial localization contradicts both the protein architecture and direct experimental evidence. Supporting Evidence: PMID:12034890 export to the extracellular space is required for its function in activating the CLV1/CLV2 receptor complex file:ARATH/CLV3/CLV3-notes.md Signal peptide 1-21; chain "Protein CLAVATA 3" 22-96. |
| GO:0010074 maintenance of meristem identity | IMP PMID:23321419 Antagonistic peptide technology for functional dissection of... | ACCEPT | Summary: Antagonistic alanine-substituted CLV3 peptides produce a dominant-negative clv3-like phenotype with enlarged shoot apical meristems and extra floral organs, confirming CLV3 acts to restrict meristem size and maintain proper stem-cell/meristem organization. This supports a role upstream of meristem maintenance. Reason: Loss/antagonism of CLV3 enlarges the SAM and disrupts meristem homeostasis; CLV3 acts upstream of meristem maintenance, a core developmental output of CLV3 signaling. Supporting Evidence: PMID:23321419 a dominant-negative clv3-like phenotype, with enlarged shoot apical meristems and increased numbers of floral organs file:ARATH/CLV3/CLV3-deep-research-falcon.md CLV3 acts non-cell-autonomously to restrict the stem cell pool |
| GO:0045087 innate immune response | IDA PMID:21499263 Stem-cell-triggered immunity through CLV3p-FLS2 signalling. | MARK AS OVER ANNOTATED | Summary: Based on Lee, Chah & Sheen (2011), which reported that CLV3p triggers FLS2/BAK1-dependent immune signaling and pathogen resistance and binds FLS2 directly. This proposed immunity function was subsequently contradicted by Segonzac et al. (2012, PMID:22923673), who could not reproduce CLV3p recognition by FLS2, and is recorded as a NOT annotation against GO:0002221 in this same dataset. The innate immune function is therefore contested and not a reliable core function of CLV3. The experimental IDA is not removed (full text reports direct binding and resistance assays), but it should not be treated as a representative function. Reason: The CLV3p-FLS2 immunity claim is disputed and could not be independently reproduced (PMID:22923673); innate immune response does not represent the established core function of CLV3, which is meristem stem-cell regulation. Retained rather than removed because the underlying experimental study cannot be overruled from the cached text alone. The Falcon deep-research synthesis independently treats apoptosis/immunity/inflammatory roles as unsupported for CLV3, corroborating this over-annotation assessment. Supporting Evidence: PMID:21499263 can trigger immune signalling and pathogen resistance via the flagellin receptor kinase FLS2 PMID:22923673 FLS2 does not recognize CLV3 and that the shoot apical meristem is immune to bacteria independently of CLV3 perception |
| GO:0033612 receptor serine/threonine kinase binding | IPI PMID:20626648 CLAVATA2 forms a distinct CLE-binding receptor complex regul... | ACCEPT | Summary: Direct ligand-binding assays show the CLV3-derived CLE peptide binds the LRR receptor serine/threonine kinases CLV1, BAM1 and BAM2 with similar nanomolar affinities (Kd ~26-36 nM). GOA carries this row four times, with WITH/FROM BAM1 (O49545), BAM2 (Q9M2Z1), CLV1 (Q9SYQ8) and CLV2 (O80809). The CLV1, BAM1 and BAM2 rows are LRR receptor kinases and support the term. The O80809 row does not, because CLV2 is a receptor-like protein with no kinase domain; CLV3 binding by CLV2 is also disputed (radioligand binding in this paper, none detected by photoaffinity labelling in PMID:25754504). This review accepts the term on the CLV1/BAM1/BAM2 evidence only. Receptor kinase binding is the core molecular function of CLV3. Reason: Experimentally demonstrated direct binding of the mature CLV3 peptide to the LRR receptor serine/threonine kinases CLV1/BAM1/BAM2, confirmed for BAM1 by photoaffinity labelling, is the defining, core molecular function of CLV3 as a peptide ligand. The CLV2 (O80809) WITH/FROM row cannot ground receptor serine/threonine kinase binding, since CLV2 lacks a kinase domain; CLV3 interaction with CLV2 is better captured by the signaling receptor binding (GO:0005102) row, with the binding dispute noted. Supporting Evidence: PMID:20626648 CLV2, CLV1 and the CLV1 homologs BAM1 and BAM2 all bind to the CLV3-derived CLE peptide with similar kinetics PMID:25754504 Further analysis showed that the receptor kinase BAM1 directly binds the CLV3 peptide. |
| GO:0033612 receptor serine/threonine kinase binding | IPI PMID:19525968 A glycopeptide regulating stem cell fate in Arabidopsis thal... | ACCEPT | Summary: Ohyama et al. showed the mature CLV3 is a 13-residue arabinosylated glycopeptide whose arabinosylation is critical for high-affinity binding to its receptor CLV1 (an LRR receptor serine/threonine kinase; WITH Q9SYQ8). This directly supports receptor serine/threonine kinase binding as the core molecular function and links the arabinosylation PTM to receptor affinity. Reason: Direct binding of the arabinosylated CLV3 glycopeptide to the LRR receptor kinase CLV1 is experimentally established; receptor kinase binding is the core molecular function. Supporting Evidence: PMID:19525968 Post-translational arabinosylation of CLV3 is critical for its biological activity and high-affinity binding to its receptor CLV1 |
| GO:0048507 meristem development | IMP PMID:16603652 Dynamic and compensatory responses of Arabidopsis shoot and ... | KEEP AS NON CORE | Summary: Altered CLV3 signaling changes meristem growth and organ allocation, demonstrating CLV3 acts upstream of meristem development. This is a correct but relatively general developmental-process annotation; the more specific maintenance/regulation of meristem terms better capture CLV3's role. Reason: Correct but general; meristem development is a broad parent of the more specific and informative meristem-maintenance and meristem-organization terms that capture CLV3's stem-cell-restricting role. Supporting Evidence: PMID:16603652 increased CLV3 signaling restricts meristem growth and promotes allocation of peripheral meristem cells into organ primordia |
| GO:0009934 regulation of meristem structural organization | IDA PMID:16902141 A plant peptide encoded by CLV3 identified by in situ MALDI-... | ACCEPT | Summary: Synthetic MCLV3 (the modified 12-aa peptide identified by in situ MALDI-TOF MS) induces shoot and root meristem consumption and differentiation, recapitulating CLV3 overexpression. This directly demonstrates that CLV3 regulates the structural organization and size of the meristem, a core developmental output of CLV3 signaling. Reason: The mature CLV3 peptide directly alters meristem structure/size (meristem consumption upon excess signaling), supporting regulation of meristem structural organization as a core process. Supporting Evidence: PMID:16902141 Synthetic MCLV3 induced shoot and root meristem consumption as cells differentiated into other organs |
| GO:0048046 apoplast | IDA PMID:12034890 CLV3 is localized to the extracellular space, where it activ... | ACCEPT | Summary: Rojo et al. demonstrated genetically and immunologically that CLV3 localizes to the apoplast and that export to the extracellular space is required for activating the CLV receptor complex. Apoplast is the most precise and directly supported localization term for CLV3 and is a core aspect of its function. Reason: Directly demonstrated apoplastic localization; this is the precise extracellular compartment in which the secreted CLV3 peptide acts as a ligand. Supporting Evidence: PMID:12034890 CLV3 localizes to the apoplast and that export to the extracellular space is required for its function in activating the CLV1/CLV2 receptor complex file:ARATH/CLV3/CLV3-deep-research-falcon.md supporting an apoplastic site of ligand action |
| GO:0007165 signal transduction | IMP PMID:10915624 Dependence of stem cell fate in Arabidopsis on a feedback lo... | KEEP AS NON CORE | Summary: CLV3 overexpression and feedback analyses show CLV3 activity drives signaling exclusively through the CLV1/CLV2 receptor kinase complex to repress WUS. This general signal transduction term is correct but is more specifically captured by GO:0007166 (cell surface receptor signaling pathway). Reason: Correct but generic; the cell-surface receptor signaling pathway term (GO:0007166) is the more informative representation of CLV3's signaling role. Supporting Evidence: PMID:10915624 CLV3 signaling occurs exclusively through a CLV1/CLV2 receptor kinase complex |
| GO:0030154 cell differentiation | IMP PMID:10915624 Dependence of stem cell fate in Arabidopsis on a feedback lo... | KEEP AS NON CORE | Summary: By restricting WUS and limiting the stem-cell pool, CLV3 promotes the differentiation of meristem cells into organ primordia, so it acts upstream of cell differentiation. The term is correct but very general; the cell-fate-commitment and meristem-organization terms capture this role more specifically. Reason: Correct but broad; CLV3's role in promoting differentiation is better represented by GO:0045168 (cell-cell signaling involved in cell fate commitment) and the meristem-regulation terms. Supporting Evidence: PMID:10915624 the CLV pathway acts by repressing the activity of the transcription factor WUSCHEL |
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Download this section (compressed HTML)Q: What protease(s) process the CLV3 precursor into the mature 12-13 residue MCLV3/CLV3p peptide in vivo, and where in the secretory pathway or apoplast does processing occur?
Suggested experts: Plant peptide hormone biochemists, Protease/proteomics specialists
Q: How do hydroxyproline arabinosylation and the C-terminal residues jointly determine receptor selectivity among CLV1, BAM1/2 and CLV2-CRN?
Suggested experts: Glycobiology researchers, Plant receptor kinase structural biologists
Q: Is the proposed CLV3p-FLS2 immune signaling a genuine endogenous function, and if so under what conditions, given the conflicting reports?
Suggested experts: Plant innate immunity researchers, Stem-cell signaling researchers
Experiment: Compare receptor binding and meristem-consumption activity of synthetic MCLV3 peptides with and without the triarabinose chain, and test in arabinosyltransferase (e.g. HPAT/RGP) mutant backgrounds, measuring Kd by quantitative binding assays and WUS repression by reporter readouts.
Hypothesis: Arabinosylation of hydroxyproline Pro-76 is required for high-affinity binding to CLV1/BAM receptors in vivo
Experiment: Use quantitative co-immunoprecipitation and ligand-binding assays in receptor single and higher-order mutants to dissect the contribution of each complex to CLV3 perception and WUS repression in the SAM.
Hypothesis: CLV1/BAM and CLV2-CRN form two parallel receptor complexes that each perceive CLV3 to control stem-cell number
Experiment: Independently repeat direct binding (radiolabeled CLV3p to FLS2), MAPK activation, and pathogen-resistance assays across multiple labs and FLS2 alleles, with rigorous peptide purity controls, to resolve the discrepancy between PMID:21499263 and PMID:22923673.
Hypothesis: The reported CLV3p-FLS2 immune signaling is not a reproducible endogenous function
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