caps

UniProt ID: A0A0S0WP14
Organism: Drosophila melanogaster
Review Status: DRAFT
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Gene 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 Review

GO Term Evidence Action Reason
GO:0007416 synapse assembly
IMP
PMID:24386266
Assessing the role of cell-surface molecules in central syna...
KEEP AS NON CORE
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.
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.
Supporting Evidence:
PMID:19270171
The nascent synaptic sites of M12 were also reduced
PMID:24386266
Caps does not have a major role in synapse formation at specific sites in R8 photoreceptor axons
GO:0036194 muscle cell projection
IDA
PMID:19270171
Target recognition at the tips of postsynaptic filopodia: ac...
ACCEPT
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.
Reason: Direct imaging evidence (IDA) for Caps at myopodia, a muscle cell projection; the term accurately captures the observed subcellular localization.
Supporting Evidence:
PMID:19270171
CAPS, expressed as a GFP-fusion protein in M12, accumulated at the tips of myopodia
GO:0035230 cytoneme
IDA
PMID:24385607
Cytoneme-mediated contact-dependent transport of the Drosoph...
ACCEPT
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.
Reason: Direct fluorescence localization (IDA) of Caps:GFP to cytonemes; colocalizes_with qualifier is appropriate for an overexpressed reporter localization.
Supporting Evidence:
PMID:24385607
Caps:GFP that was expressed in trachea was detected in ASP cytonemes, and concentrated at the tips
GO:0007436 larval salivary gland morphogenesis
IMP
PMID:19064711
A targeted gain-of-function screen identifies genes affectin...
KEEP AS NON CORE
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.
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.
Supporting Evidence:
PMID:19064711
The analysis of caps and tartan mutant phenotypes suggests a role for these genes in salivary gland morphogenesis
GO:0007156 homophilic cell-cell adhesion
IDA
PMID:16423695
Regulation of layer-specific targeting by reciprocal express...
ACCEPT
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.
Reason: Direct cell-aggregation assay (IDA) demonstrates homophilic adhesion; this captures a core molecular behavior of Caps.
Supporting Evidence:
PMID:16423695
CAPS promotes homophilic cell adhesion in transfected S2 cells
GO:0072499 photoreceptor cell axon guidance
IMP
PMID:16423695
Regulation of layer-specific targeting by reciprocal express...
KEEP AS NON CORE
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.
Reason: Experimentally supported (IMP) but a tissue-specific, low-penetrance/redundant instance of the broader target-recognition activity; better represented as non-core.
Supporting Evidence:
PMID:16423695
caps loss-of-function mutations cause local targeting errors by R8 axons, including layer change
PMID:24386266
Caps has a marginal role in the guidance of R8 photoreceptor axons and is not redundant with Tartan.
GO:0008045 motor neuron axon guidance
IMP
PMID:18817735
A screen of cell-surface molecules identifies leucine-rich r...
ACCEPT
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.
Reason: Strong experimental support (IMP) for Caps in motor-axon guidance/targeting; represents the best-studied context of the gene's core recognition function.
Supporting Evidence:
PMID:18817735
Capricious (Caps) is a leucine-rich repeat (LRR) protein that is expressed on muscle 12
PMID:18817735
The penetrances of the ISNb and SNa phenotypes (55% and 60%, respectively) in double mutant embryos were roughly doubled relative to
GO:0035147 branch fusion, open tracheal system
IMP
PMID:16764850
Distinct functions of the leucine-rich repeat transmembrane ...
KEEP AS NON CORE
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.
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.
Supporting Evidence:
PMID:16764850
Capricious is specifically localized on the surface of bridge-cells and facilitates the outgrowing dorsal trunk cells of adjacent metameres toward each other
GO:0007155 cell adhesion
NAS
PMID:12717815
Pattern formation in the Drosophila wing: The development of...
KEEP AS NON CORE
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.
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.
Supporting Evidence:
PMID:19064711
It has been suggested that Caps and Trn act as homophilic or heterophilic adhesion receptors
PMID:16423695
CAPS promotes homophilic cell adhesion in transfected S2 cells
GO:0007411 axon guidance
IMP
PMID:11677048
Axon guidance of Drosophila SNb motoneurons depends on the c...
ACCEPT
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.
Reason: Experimentally supported (IMP) parent term for Caps' core axon-guidance/target-recognition role; a legitimate broader annotation alongside the more specific GO:0008045.
Supporting Evidence:
PMID:11677048
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
GO:0016477 cell migration
TAS
PMID:12508275
Size isn't everything.
KEEP AS NON CORE
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.
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.
Supporting Evidence:
PMID:16764850
Capricious is specifically localized on the surface of bridge-cells and facilitates the outgrowing dorsal trunk cells of adjacent metameres toward each other.
PMID:16764850
We propose that Capricious contributes to the instructive role of bridge-cells
GO:0098632 cell-cell adhesion mediator activity
IDA
PMID:16423695
Regulation of layer-specific targeting by reciprocal express...
NEW
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).
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.
Supporting Evidence:
PMID:16423695
CAPS promotes homophilic cell adhesion in transfected S2 cells
GO:0005886 plasma membrane
IDA
PMID:16423695
Regulation of layer-specific targeting by reciprocal express...
NEW
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).
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.
Supporting Evidence:
PMID:16423695
Capricious (CAPS), a transmembrane protein with leucine-rich repeats (LRRs)
PMID:11677048
which encodes a cell-surface protein

Core Functions

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.

Directly Involved In:
Cellular Locations:
Supporting Evidence:
  • PMID:16423695
    CAPS promotes homophilic cell adhesion in transfected S2 cells
  • PMID:19064711
    It has been suggested that Caps and Trn act as homophilic or heterophilic adhesion receptors

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.

Supporting Evidence:
  • PMID:11677048
    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
  • PMID:19270171
    CAPS, expressed as a GFP-fusion protein in M12, accumulated at the tips of myopodia

References

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Suggested Questions for Experts

Q: 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?

Q: 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

Experiment: 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.

Experiment: 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.

πŸ“š Additional Documentation

Notes

(caps-notes.md)

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