id: A0A0S0WP14 gene_symbol: caps product_type: PROTEIN status: DRAFT taxon: id: NCBITaxon:7227 label: Drosophila melanogaster description: >- capricious (caps; CG11282; FBgn0023095) is a Drosophila melanogaster single-pass type I transmembrane protein of the leucine-rich-repeat (LRR) cell-surface receptor class. Its extracellular region is built from a horseshoe-shaped LRR array (multiple LRR repeats plus an LRR C-terminal cap) followed by a single transmembrane helix and a cytoplasmic tail. Caps is the paralog of Tartan (Trn), with which it shares ~65% extracellular-domain identity and largely overlapping, partially redundant functions. Biochemically Caps behaves as a cell-surface adhesion/recognition molecule: it promotes homophilic cell adhesion in cultured cells and is also proposed to engage heterophilic partners. Its best-characterized role is as a target-recognition label in the nervous system, where reciprocal expression of Caps on motor neurons and their target muscles (and on photoreceptor axons and their recipient layers) directs selective synaptic matching; Caps concentrates at the tips of cellular projections such as myopodia (postsynaptic muscle filopodia) where initial neuromuscular contacts form. Beyond neural wiring, the same adhesion/recognition activity is deployed in tracheal dorsal-trunk branch fusion (Caps on mesodermal bridge cells), salivary-gland tubulogenesis, imaginal-disc compartment-affinity boundaries, and cytoneme-mediated signaling. Caps thus functions broadly as an LRR cell-adhesion molecule that confers cell-type-specific surface identity used for adhesion, boundary formation, and synaptic/axonal target selection. existing_annotations: - term: id: GO:0007416 label: synapse assembly evidence_type: IMP original_reference_id: PMID:24386266 qualifier: involved_in review: summary: >- Caps contributes to synapse formation only indirectly, through its target-recognition role. At the NMJ, caps (and caps trn) mutants have fewer myopodia-growth-cone contacts and reduced nascent synaptic sites (PMID:19270171). However, the cited visual-system study concluded that Caps is largely dispensable for synaptogenesis proper in R8 photoreceptors, distinguishing target recognition from synapse assembly. Keep as a non-core, downstream consequence of Caps-mediated partner matching rather than a core synapse-assembly activity. action: KEEP_AS_NON_CORE reason: >- The annotated function is real at the NMJ but secondary to Caps' core adhesion/recognition role, and the cited reference itself argues against a major direct synaptogenic role in the photoreceptor system. Better supported as non-core. supported_by: - reference_id: PMID:19270171 supporting_text: The nascent synaptic sites of M12 were also reduced - reference_id: PMID:24386266 supporting_text: Caps does not have a major role in synapse formation at specific sites in R8 photoreceptor axons - term: id: GO:0036194 label: muscle cell projection evidence_type: IDA original_reference_id: PMID:19270171 qualifier: located_in review: summary: >- A Caps-GFP fusion expressed in muscle 12 accumulates at the tips of myopodia (the postsynaptic filopodia of body-wall muscles), directly documenting Caps localization to a muscle cell projection. This localization is mechanistically tied to Caps' function in sensing and stabilizing contacts with the correct presynaptic partner. action: ACCEPT reason: >- Direct imaging evidence (IDA) for Caps at myopodia, a muscle cell projection; the term accurately captures the observed subcellular localization. supported_by: - reference_id: PMID:19270171 supporting_text: CAPS, expressed as a GFP-fusion protein in M12, accumulated at the tips of myopodia - term: id: GO:0035230 label: cytoneme evidence_type: IDA original_reference_id: PMID:24385607 qualifier: colocalizes_with review: summary: >- In the tracheal air-sac primordium, a tracheally expressed Caps:GFP fusion is detected along cytonemes and concentrated at their tips, and caps is required for cytoneme-mediated Dpp reception. This supports colocalization of Caps with cytonemes, consistent with its general enrichment at the tips of cellular projections. action: ACCEPT reason: >- Direct fluorescence localization (IDA) of Caps:GFP to cytonemes; colocalizes_with qualifier is appropriate for an overexpressed reporter localization. supported_by: - reference_id: PMID:24385607 supporting_text: Caps:GFP that was expressed in trachea was detected in ASP cytonemes, and concentrated at the tips - term: id: GO:0007436 label: larval salivary gland morphogenesis evidence_type: IMP original_reference_id: PMID:19064711 qualifier: involved_in review: summary: >- caps was recovered in a salivary-gland (fork head-GAL4) gain-of-function tubulogenesis screen, and gain- versus loss-of-function comparison implicates it in salivary gland morphogenesis. This is one of several tissue-specific developmental contexts in which Caps' adhesion/ recognition activity is deployed, so it is retained as a non-core developmental role. action: KEEP_AS_NON_CORE reason: >- Experimentally supported (IMP) developmental role, but peripheral to the core LRR adhesion/target-recognition function; appropriate to keep as non-core for this pleiotropic gene. supported_by: - reference_id: PMID:19064711 supporting_text: The analysis of caps and tartan mutant phenotypes suggests a role for these genes in salivary gland morphogenesis - term: id: GO:0007156 label: homophilic cell-cell adhesion evidence_type: IDA original_reference_id: PMID:16423695 qualifier: involved_in review: summary: >- Caps promotes homophilic cell adhesion when expressed in cultured S2 cells, providing direct biochemical/cell-based evidence for a homophilic adhesion activity. This is central to Caps' proposed mechanism as a layer-/target-specific cell adhesion molecule, although later work indicates that in vivo axon-target recognition is not exclusively homophilic. action: ACCEPT reason: >- Direct cell-aggregation assay (IDA) demonstrates homophilic adhesion; this captures a core molecular behavior of Caps. supported_by: - reference_id: PMID:16423695 supporting_text: CAPS promotes homophilic cell adhesion in transfected S2 cells - term: id: GO:0072499 label: photoreceptor cell axon guidance evidence_type: IMP original_reference_id: PMID:16423695 qualifier: involved_in review: summary: >- caps is reciprocally expressed in R8 axons and their target layer; caps loss causes local R8 targeting errors and ectopic caps in R7 redirects R7 axons to the R8 recipient layer. A later reassessment found the endogenous requirement modest ("marginal role") and redundant, so this is a genuine but non-core, context-specific manifestation of Caps' target-recognition function. action: KEEP_AS_NON_CORE reason: >- Experimentally supported (IMP) but a tissue-specific, low-penetrance/redundant instance of the broader target-recognition activity; better represented as non-core. supported_by: - reference_id: PMID:16423695 supporting_text: caps loss-of-function mutations cause local targeting errors by R8 axons, including layer change - reference_id: PMID:24386266 supporting_text: Caps has a marginal role in the guidance of R8 photoreceptor axons and is not redundant with Tartan. - term: id: GO:0008045 label: motor neuron axon guidance evidence_type: IMP original_reference_id: PMID:18817735 qualifier: involved_in review: summary: >- Caps is expressed on subsets of body-wall muscles (including muscle 12) and functions with its paralog Trn in the guidance and target selection of ISNb/SNa motor axons; trn caps double mutants roughly double the ISNb/SNa guidance-defect penetrance relative to single mutants, showing a genuine (partially redundant) caps contribution. This is a core, well-characterized function of Caps. action: ACCEPT reason: >- Strong experimental support (IMP) for Caps in motor-axon guidance/targeting; represents the best-studied context of the gene's core recognition function. supported_by: - reference_id: PMID:18817735 supporting_text: Capricious (Caps) is a leucine-rich repeat (LRR) protein that is expressed on muscle 12 - reference_id: PMID:18817735 supporting_text: The penetrances of the ISNb and SNa phenotypes (55% and 60%, respectively) in double mutant embryos were roughly doubled relative to - term: id: GO:0035147 label: branch fusion, open tracheal system evidence_type: IMP original_reference_id: PMID:16764850 qualifier: involved_in review: summary: >- Caps is displayed on mesodermal bridge-cells and instructs the outgrowing dorsal-trunk cells of adjacent tracheal metameres toward each other, contributing to branch interconnection/ fusion; Caps requires both its extracellular and intracellular domains for this role. A tissue-specific developmental deployment of the adhesion/recognition activity, retained as non-core. action: KEEP_AS_NON_CORE reason: >- Experimentally supported (IMP) developmental role in tracheal branch fusion, but a specialized context of the core surface-recognition function rather than the central activity itself. supported_by: - reference_id: PMID:16764850 supporting_text: Capricious is specifically localized on the surface of bridge-cells and facilitates the outgrowing dorsal trunk cells of adjacent metameres toward each other - term: id: GO:0007155 label: cell adhesion evidence_type: NAS original_reference_id: PMID:12717815 qualifier: involved_in review: summary: >- Cell adhesion is a correct, if very general, description of Caps activity: Caps is an LRR cell-surface adhesion molecule that promotes homophilic adhesion (PMID:16423695) and is proposed to act as a homophilic/heterophilic adhesion receptor (PMID:19064711). The cited reference (an abstract-only wing-vein-development review) does not itself discuss caps, and a more specific term (homophilic cell-cell adhesion, GO:0007156) is already annotated. Keep as a broad, non-core parent. action: KEEP_AS_NON_CORE reason: >- The function is accurate but general and better captured by the specific homophilic adhesion annotation; the NAS reference is a review that does not directly support the caps claim, so this is retained only as a broad non-core term rather than accepted as a core annotation. supported_by: - reference_id: PMID:19064711 supporting_text: It has been suggested that Caps and Trn act as homophilic or heterophilic adhesion receptors - reference_id: PMID:16423695 supporting_text: CAPS promotes homophilic cell adhesion in transfected S2 cells - term: id: GO:0007411 label: axon guidance evidence_type: IMP original_reference_id: PMID:11677048 qualifier: involved_in review: summary: >- Caps functions as a cell-surface recognition molecule in motor-axon guidance, regulating the selective connection between the SNb motoneuron RP5 and muscle 12. This is the general (parent) axon-guidance term for the same activity captured more specifically by motor neuron axon guidance (GO:0008045); accepted as a core function. action: ACCEPT reason: >- Experimentally supported (IMP) parent term for Caps' core axon-guidance/target-recognition role; a legitimate broader annotation alongside the more specific GO:0008045. supported_by: - reference_id: PMID:11677048 supporting_text: functions as a recognition molecule in motor axon guidance, regulating the formation of the selective connections between the SNb-derived motoneuron RP5 and muscle 12 - term: id: GO:0016477 label: cell migration evidence_type: TAS original_reference_id: PMID:12508275 qualifier: involved_in review: summary: >- Caps contributes to cell migration non-cell-autonomously: it is localized on the surface of mesodermal bridge-cells and instructs the outgrowth of dorsal trunk branch cells toward each other during tracheal network formation. This is a real but peripheral, context-specific role rather than a core function, so it is retained as non-core. The identical annotation (GO:0016477, TAS, PMID:12508275) is present in trn-goa.tsv and is adjudicated the same way in the trn review. action: KEEP_AS_NON_CORE reason: >- The general 'cell migration' term is supported by the concrete role of Capricious as an instructive bridge-cell cue for outgrowing tracheal branch cells; it captures a real but indirect and non-core aspect of caps function. The original TAS reference is a short commentary that does not itself discuss caps, so supporting evidence is drawn from the tracheal study instead. Kept consistent with the trn review, which handles the same GOA row identically. supported_by: - reference_id: PMID:16764850 supporting_text: >- Capricious is specifically localized on the surface of bridge-cells and facilitates the outgrowing dorsal trunk cells of adjacent metameres toward each other. - reference_id: PMID:16764850 supporting_text: >- We propose that Capricious contributes to the instructive role of bridge-cells - term: id: GO:0098632 label: cell-cell adhesion mediator activity evidence_type: IDA original_reference_id: PMID:16423695 qualifier: enables review: summary: >- The GOA set contains no molecular-function annotation, yet Caps' central activity is cell-surface adhesion mediation: expression of Caps in otherwise non-adhesive S2 cells induces homophilic aggregation, demonstrating that Caps directly mediates cell-cell adhesion. Proposed as a NEW molecular-function annotation to capture the core activity underlying the many BP contexts (target recognition, boundary formation). action: NEW reason: >- Adds the missing core molecular function. Direct cell-aggregation assay (IDA) shows Caps mediates homophilic cell-cell adhesion; a specific MF term is more informative than the generic cell-adhesion BP terms alone. supported_by: - reference_id: PMID:16423695 supporting_text: CAPS promotes homophilic cell adhesion in transfected S2 cells - term: id: GO:0005886 label: plasma membrane evidence_type: IDA original_reference_id: PMID:16423695 qualifier: located_in review: summary: >- Caps is a single-pass transmembrane protein displayed at the cell surface, consistent with its role as a cell-surface adhesion/recognition molecule. UniProt annotates cell periphery (GO:0071944) by ARBA. Added as a NEW plasma-membrane localization to make the core cellular location explicit, since the GOA set only contained projection-specific components (muscle cell projection, cytoneme). action: NEW reason: >- Captures the core plasma-membrane localization of this transmembrane cell-surface protein, which is implied by but not explicit in the existing component annotations. supported_by: - reference_id: PMID:16423695 supporting_text: Capricious (CAPS), a transmembrane protein with leucine-rich repeats (LRRs) - reference_id: PMID:11677048 supporting_text: which encodes a cell-surface protein core_functions: - description: >- Acts as an LRR cell-surface adhesion/recognition molecule that mediates cell-cell adhesion (demonstrated as homophilic aggregation in cultured cells; also proposed heterophilic), conferring cell-type-specific surface identity at the plasma membrane. supported_by: - reference_id: PMID:16423695 supporting_text: CAPS promotes homophilic cell adhesion in transfected S2 cells - reference_id: PMID:19064711 supporting_text: It has been suggested that Caps and Trn act as homophilic or heterophilic adhesion receptors molecular_function: id: GO:0098632 label: cell-cell adhesion mediator activity directly_involved_in: - id: GO:0007156 label: homophilic cell-cell adhesion locations: - id: GO:0005886 label: plasma membrane - description: >- Serves as a synaptic/axonal target-recognition label: reciprocal Caps expression on motor neurons and their target muscles (and on photoreceptor axons and recipient layers) directs selective partner matching. Caps concentrates at the tips of postsynaptic myopodia where initial neuromuscular contacts form, and functions partially redundantly with its paralog Tartan in ISNb/SNa motor-axon guidance and target selection. supported_by: - reference_id: PMID:11677048 supporting_text: functions as a recognition molecule in motor axon guidance, regulating the formation of the selective connections between the SNb-derived motoneuron RP5 and muscle 12 - reference_id: PMID:19270171 supporting_text: CAPS, expressed as a GFP-fusion protein in M12, accumulated at the tips of myopodia molecular_function: id: GO:0098632 label: cell-cell adhesion mediator activity directly_involved_in: - id: GO:0008045 label: motor neuron axon guidance - id: GO:0007411 label: axon guidance locations: - id: GO:0036194 label: muscle cell projection - id: GO:0005886 label: plasma membrane proposed_new_terms: [] suggested_questions: - question: >- Does Caps have an obligate heterophilic binding partner (a dedicated receptor/ligand) in addition to its homophilic activity, and is this the "common receptor" shared with Tartan? - question: >- Does the Caps cytoplasmic tail transduce an intracellular signal (e.g. during target recognition or tracheal outgrowth), or does it act mainly by regulating adhesion/localization? suggested_experiments: - description: >- Biochemically identify in vivo Caps binding partners (e.g. by proximity labeling or affinity purification from neural/tracheal tissue) to test homophilic versus heterophilic engagement and the proposed shared Caps/Trn receptor. - description: >- Structure-guided separation-of-function alleles of the Caps ectodomain versus cytoplasmic tail, assayed across NMJ target selection, photoreceptor layer targeting, and tracheal branch fusion, to determine which activities require intracellular signaling. references: - id: PMID:11677048 title: Axon guidance of Drosophila SNb motoneurons depends on the cooperative action of muscular Krüppel and neuronal capricious activities. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: >- Abstract-only cache; establishes Caps as a cell-surface recognition molecule regulating the RP5 motoneuron-muscle 12 connection. Directly supports the axon-guidance annotations. - id: PMID:12508275 title: Size isn't everything. findings: [] reference_review: relevance: LOW correctness: MISCITED review_notes: >- Abstract-only Bioessays review on tissue size/shape control; the abstract does not mention caps or cell migration. It is the TAS basis for GO:0016477 but is only background/contextual for caps - the real support for a migration role comes from the tracheal study (PMID:16764850). - id: PMID:12717815 title: 'Pattern formation in the Drosophila wing: The development of the veins.' findings: [] reference_review: relevance: LOW correctness: MISCITED review_notes: >- Abstract-only Bioessays review on wing-vein patterning; the abstract does not mention caps. Cited as NAS support for GO:0007155 (cell adhesion); the general adhesion function is correct for caps but is not directly supported by this review - a weak/likely-inappropriate NAS citation, adjudicated identically in the trn review, which carries the same GOA row. - id: PMID:16423695 title: Regulation of layer-specific targeting by reciprocal expression of a cell adhesion molecule, capricious. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: >- Abstract-only cache but content-verified: demonstrates Caps homophilic adhesion in S2 cells and reciprocal R8/R7 layer-specific targeting. Supports the homophilic-adhesion MF and photoreceptor-targeting annotations. - id: PMID:16764850 title: Distinct functions of the leucine-rich repeat transmembrane proteins capricious and tartan in the Drosophila tracheal morphogenesis. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: >- Abstract-only cache; shows Caps on bridge-cells instructing dorsal-trunk branch fusion and requiring both extra- and intracellular domains. Supports GO:0035147. - id: PMID:18817735 title: A screen of cell-surface molecules identifies leucine-rich repeat proteins as key mediators of synaptic target selection. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: >- Full text available and reviewed; quantifies trn caps redundancy in ISNb/SNa motor-axon targeting and Caps expression on muscle 12. Supports GO:0008045. - id: PMID:19064711 title: A targeted gain-of-function screen identifies genes affecting salivary gland morphogenesis/tubulogenesis in Drosophila. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: >- Full text available and reviewed; implicates caps/trn in salivary gland morphogenesis and summarizes the homophilic/heterophilic adhesion-receptor hypothesis. Supports GO:0007436. - id: PMID:19270171 title: 'Target recognition at the tips of postsynaptic filopodia: accumulation and function of Capricious.' findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: >- Abstract-only cache but content-verified: Caps-GFP accumulates at myopodia tips and caps/ caps trn mutants show fewer myopodia-growth-cone contacts and reduced nascent synaptic sites. Supports the muscle cell projection localization and the NMJ synapse-formation contribution. - id: PMID:24385607 title: Cytoneme-mediated contact-dependent transport of the Drosophila decapentaplegic signaling protein. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: >- Full text available and reviewed; Caps:GFP localizes to ASP cytonemes (enriched at tips) and caps is required for cytoneme-mediated Dpp reception. Supports GO:0035230. - id: PMID:24386266 title: Assessing the role of cell-surface molecules in central synaptogenesis in the Drosophila visual system. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: >- Full text available and reviewed; reassesses Caps in R8 targeting/synaptogenesis, finding a marginal, non-homophilic guidance role and no major direct role in R8 synapse formation. Important nuance for the synapse-assembly and photoreceptor annotations.