Sticks and stones (Sns) is a transmembrane immunoglobulin-superfamily adhesion receptor of the nephrin subfamily (PANTHER PTHR11640:SF136, shared with its paralog Hibris, vertebrate nephrin/NPHS1 and C. elegans SYG-2). Its extracellular region of Ig and fibronectin type III domains binds the Kirre/Neph1-family proteins Dumbfounded/Kirre and Roughest in trans, forming heterophilic adhesion complexes. On fusion-competent myoblasts Sns recognizes founder cells and is required for myoblast fusion and body-wall and visceral muscle formation, with its tyrosine-phosphorylated cytoplasmic tail linking adhesion to the fusion machinery. In nephrocytes Sns and Kirre localize to and are required to assemble the nephrin-like filtration diaphragm that controls protein uptake. The same adhesion system contributes to ommatidial separation in the eye, spacing of wing-margin sensory bristles, and somatic cyst-cell support of spermatid maturation.
IMP PMID:20599904 Preferential adhesion maintains separation of ommatidia in t...
KEEP AS NON CORE
Summary: Sns participates in the differential adhesion and cellular arrangement of the developing compound eye. Retain this tissue-specific developmental association as noncore relative to its cell-adhesion mechanism; the evidence does not establish an independent photoreceptor fate-specification activity.
Reason: Sns participates in the differential adhesion and cellular arrangement of the developing compound eye. Retain this tissue-specific developmental association as noncore relative to its cell-adhesion mechanism; the evidence does not establish an independent photoreceptor fate-specification activity.
NAS PMID:20599904 Preferential adhesion maintains separation of ommatidia in t...
MODIFY
Summary: ComplexPortal NAS for the Rst-Sns/Kirre-Sns adhesion complexes. The cited study shows that Sns and Hbs expressed in primary pigment cells make ommatidia preferentially adhere to interommatidial cells, keeping ommatidia apart; it does not show a role in photoreceptor fate specification or differentiation.
Reason: The process supported by the reference is morphogenetic patterning of the eye (ommatidial separation by preferential adhesion), already captured by GO:0001745 compound eye morphogenesis (IMP, same paper). Photoreceptor cell differentiation is a lateral mis-statement of that outcome, so the row is redirected to the morphogenesis term the gene already carries.
IPI PMID:18971929 The insect nephrocyte is a podocyte-like cell with a filtrat...
REMOVE
Summary: Yeast two-hybrid shows the Sns intracellular domain binding the Mec-2 (podocin) C-terminal cytoplasmic domain. The interaction is real but bare protein binding conveys no functional information.
Reason: Per the GO:0005515 policy, an uninformative bare protein-binding row is removed; removal does not dispute the reported Sns-Mec-2 interaction. No more informative MF (e.g. a scaffold or adaptor activity) is demonstrated for Sns in this assay, and the functional consequence is captured by the nephrocyte diaphragm location and assembly annotations.
IPI PMID:23827685 An extracellular interactome of immunoglobulin and LRR prote...
MODIFY
Summary: Sns binds the extracellular adhesion protein Roughest; the interaction is part of the conserved nephrin/NEPH adhesion system. Cell adhesion molecule binding is more informative than generic protein binding, and the Drosophila heterocomplex is directly measured.
Reason: Sns binds the extracellular adhesion protein Roughest; the interaction is part of the conserved nephrin/NEPH adhesion system. Cell adhesion molecule binding is more informative than generic protein binding, and the Drosophila heterocomplex is directly measured.
IPI PMID:23827685 An extracellular interactome of immunoglobulin and LRR prote...
REMOVE
Summary: The extracellular interactome screen (ECIA, pentamerized ectodomains) reports an Sns-Unc-5 binding pair. Its physiological relevance has not been tested, and bare protein binding conveys no functional information.
Reason: Per the GO:0005515 policy the uninformative bare protein-binding row is removed; the interactome observation is not disputed. Unc-5 is a netrin receptor and no adhesion or guidance function of an Sns-Unc-5 pair is established, so neither cell adhesion molecule binding nor a signaling-receptor term can be justified as a replacement.
IPI PMID:24485456 Extracellular architecture of the SYG-1/SYG-2 adhesion compl...
MODIFY
Summary: Sns binds the extracellular adhesion protein Roughest; the interaction is part of the conserved nephrin/NEPH adhesion system. Cell adhesion molecule binding is more informative than generic protein binding, and the Drosophila heterocomplex is directly measured.
Reason: Sns binds the extracellular adhesion protein Roughest; the interaction is part of the conserved nephrin/NEPH adhesion system. Cell adhesion molecule binding is more informative than generic protein binding, and the Drosophila heterocomplex is directly measured.
Summary: Sns is a cell-surface adhesion molecule enriched at myoblast contacts and nephrocyte junctions. Primary localization supports the membrane/junction assignment independently of automated location propagation.
Reason: Sns is a cell-surface adhesion molecule enriched at myoblast contacts and nephrocyte junctions. Primary localization supports the membrane/junction assignment independently of automated location propagation.
Sns and Kirre proteins localize to the ND at the entry point into the labyrinthine channels and, like their vertebrate counterparts, are essential for its formation.
IDA PMID:10859168 Drosophila SNS, a member of the immunoglobulin superfamily t...
ACCEPT
Summary: Sns is a cell-surface adhesion molecule enriched at myoblast contacts and nephrocyte junctions. Primary localization supports the membrane/junction assignment independently of automated location propagation.
Reason: Sns is a cell-surface adhesion molecule enriched at myoblast contacts and nephrocyte junctions. Primary localization supports the membrane/junction assignment independently of automated location propagation.
Sns and Kirre proteins localize to the ND at the entry point into the labyrinthine channels and, like their vertebrate counterparts, are essential for its formation.
Summary: Sns is a cell-surface adhesion molecule enriched at myoblast contacts and nephrocyte junctions. Primary localization supports the membrane/junction assignment independently of automated location propagation.
Reason: Sns is a cell-surface adhesion molecule enriched at myoblast contacts and nephrocyte junctions. Primary localization supports the membrane/junction assignment independently of automated location propagation.
Sns and Kirre proteins localize to the ND at the entry point into the labyrinthine channels and, like their vertebrate counterparts, are essential for its formation.
IDA PMID:18971929 The insect nephrocyte is a podocyte-like cell with a filtrat...
ACCEPT
Summary: Immunogold and confocal localization place Sns specifically at the nephrocyte diaphragm together with Duf/Kirre.
Reason: Direct localization supports this specific junction; Sns is a structural adhesion component of the nephrocyte diaphragm by analogy with nephrin at the podocyte slit diaphragm.
Both Sns and Duf specifically localise to the nephrocyte diaphragm (Fig 2q-s) and double labelling reveals close colocalisation between the two proteins (Fig.
Sns and Kirre proteins localize to the ND at the entry point into the labyrinthine channels and, like their vertebrate counterparts, are essential for its formation.
IDA PMID:19515699 Sns and Kirre, the Drosophila orthologs of Nephrin and Neph1...
ACCEPT
Summary: Sns is a structural cell-adhesion component of the nephrocyte diaphragm. Direct localization and loss-of-function studies support its presence and role at this filtration junction.
Reason: Sns is a structural cell-adhesion component of the nephrocyte diaphragm. Direct localization and loss-of-function studies support its presence and role at this filtration junction.
Sns and Kirre proteins localize to the ND at the entry point into the labyrinthine channels and, like their vertebrate counterparts, are essential for its formation.
IDA PMID:38878170 Phospholipid scramblase 1: an essential component of the nep...
ACCEPT
Summary: In the Scramb1 study, Sns colocalizes with Duf, Pyd and Scramb1 in strands that form the nephrocyte slit diaphragm and localizes to cell-cell contact sites.
Reason: Independent localization of Sns at the nephrocyte diaphragm consistent with the earlier studies.
Finally, 18 h after the temperature switch, most nephrocytes were covered by a loose network of strands containing Duf, Sns, Pyd and Scramb1-A-V5, similar to the SD fingerprint pattern observed in the wild-type but less regular and dense, indicating an already significant rescue of the phenotype (Fig.
Sns and Kirre proteins localize to the ND at the entry point into the labyrinthine channels and, like their vertebrate counterparts, are essential for its formation.
IGI PMID:19515699 Sns and Kirre, the Drosophila orthologs of Nephrin and Neph1...
UNDECIDED
Summary: IGI with kirre in garland cell nephrocytes. The accessible abstract shows Sns and Kirre are co-expressed in GCNs and are required for GCN adhesion and fusion, but does not show Sns-Sns trans binding.
Reason: Homophilic adhesion requires identical molecules on both cells. The IGI with kirre and the known Sns-Kirre trans interaction point to heterophilic adhesion between co-expressing cells (homotypic cells, heterophilic molecules), but the full text, which the curator read, is not available here, so the homophilic claim can be neither confirmed nor rejected.
IDA PMID:19270174 The immunoglobulin superfamily member Hbs functions redundan...
ACCEPT
Summary: Sns on fusion-competent myoblasts engages Kirre/Roughest on founder cells, directly supporting heterophilic recognition and adhesion. This adhesive mechanism also supports specialized nephrocyte contacts.
Reason: Sns on fusion-competent myoblasts engages Kirre/Roughest on founder cells, directly supporting heterophilic recognition and adhesion. This adhesive mechanism also supports specialized nephrocyte contacts.
Sns and Kirre proteins localize to the ND at the entry point into the labyrinthine channels and, like their vertebrate counterparts, are essential for its formation.
IMP PMID:15955848 A positive feedback loop between Dumbfounded and Rolling peb...
ACCEPT
Summary: Sns on fusion-competent myoblasts is the heterophilic adhesion partner of Duf/Kirre on founder cells; in sns mutants founder-FCM contact is rarely seen.
Reason: The cited study uses sns mutants to show that founder-FCM adhesion depends on Sns, consistent with heterophilic Duf-Sns adhesion established by binding and cell-aggregation studies. This is a core process of the gene.
As Rols7 translocation and D-Titin recruitment occur even in the absence of sns, where random contact between founders and fcm is rarely seen, it has been postulated that these events might be constitutive thereby implicating the presence of preformed sites specialized for fusion on the founder cell membrane (Menon and Chia, 2001).
IMP PMID:21652648 The WASp-based actin polymerization machinery is required in...
KEEP AS NON CORE
Summary: Sns participates in the somatic support-cell machinery required for spermatid maturation/release. Retain this developmental role without implying a sperm-intrinsic enzymatic function.
Reason: Sns participates in the somatic support-cell machinery required for spermatid maturation/release. Retain this developmental role without implying a sperm-intrinsic enzymatic function.
IMP PMID:15955848 A positive feedback loop between Dumbfounded and Rolling peb...
ACCEPT
Summary: Sns is required on fusion-competent myoblasts for their adhesion to founder cells and subsequent muscle-fiber formation. The defining unfused-myoblast phenotype and receptor-ligand mechanism independently establish the gene-level myoblast-fusion role.
Reason: Sns is required on fusion-competent myoblasts for their adhesion to founder cells and subsequent muscle-fiber formation. The defining unfused-myoblast phenotype and receptor-ligand mechanism independently establish the gene-level myoblast-fusion role.
The Drosophila sticks-and-stones (sns) locus was identified on the basis of its mutant phenotype, the complete absence of body wall muscles and corresponding presence of unfused myoblasts.
IMP PMID:18003739 SCAR/WAVE and Arp2/3 are crucial for cytoskeletal remodeling...
ACCEPT
Summary: Sns is required on fusion-competent myoblasts for their adhesion to founder cells and subsequent muscle-fiber formation. The defining unfused-myoblast phenotype and receptor-ligand mechanism independently establish the gene-level myoblast-fusion role.
Reason: Sns is required on fusion-competent myoblasts for their adhesion to founder cells and subsequent muscle-fiber formation. The defining unfused-myoblast phenotype and receptor-ligand mechanism independently establish the gene-level myoblast-fusion role.
The Drosophila sticks-and-stones (sns) locus was identified on the basis of its mutant phenotype, the complete absence of body wall muscles and corresponding presence of unfused myoblasts.
IMP PMID:19270174 The immunoglobulin superfamily member Hbs functions redundan...
ACCEPT
Summary: Sns is required on fusion-competent myoblasts for their adhesion to founder cells and subsequent muscle-fiber formation. The defining unfused-myoblast phenotype and receptor-ligand mechanism independently establish the gene-level myoblast-fusion role.
Reason: Sns is required on fusion-competent myoblasts for their adhesion to founder cells and subsequent muscle-fiber formation. The defining unfused-myoblast phenotype and receptor-ligand mechanism independently establish the gene-level myoblast-fusion role.
The Drosophila sticks-and-stones (sns) locus was identified on the basis of its mutant phenotype, the complete absence of body wall muscles and corresponding presence of unfused myoblasts.
IMP PMID:11744371 The formation of syncytia within the visceral musculature of...
KEEP AS NON CORE
Summary: Mutations in sns disrupt fusion-dependent visceral muscle development. This is a tissue-specific consequence of its conserved adhesive myoblast-fusion mechanism.
Reason: Mutations in sns disrupt fusion-dependent visceral muscle development. This is a tissue-specific consequence of its conserved adhesive myoblast-fusion mechanism.
Mutations of genes that are involved in somatic myoblast fusion, such as sns, dumbfounded (duf) or myoblast city (mbc), also cause severe defects within the visceral musculature.
IGI PMID:26053791 The Cell Adhesion Molecules Roughest, Hibris, Kin of Irre an...
KEEP AS NON CORE
Summary: Sns contributes to positioning of sensory-bristle precursors through tissue adhesion. This specific morphogenesis role is retained as noncore relative to its underlying cell-recognition mechanism.
Reason: Sns contributes to positioning of sensory-bristle precursors through tissue adhesion. This specific morphogenesis role is retained as noncore relative to its underlying cell-recognition mechanism.
Summary: ARBA-derived broad developmental process. True of Sns, but entailed by more specific experimentally supported process terms retained in this review.
Reason: The term is an ancestor of compound eye morphogenesis (GO:0001745) and chaeta morphogenesis (GO:0008407), which are retained in this review with gene-specific IMP/IGI evidence, so it adds no information. The ARBA rule is not itself used as support.
The Drosophila sticks-and-stones (sns) locus was identified on the basis of its mutant phenotype, the complete absence of body wall muscles and corresponding presence of unfused myoblasts.
Summary: Sns is a transmembrane cell-surface adhesion receptor; experiments localize it to the plasma membrane at myoblast contact sites and at the nephrocyte diaphragm.
Reason: Membrane is correct but less specific than the evidence supports. The gene already carries plasma membrane (IDA, IBA), so this SubCell-mapped row is refined to GO:0005886 plasma membrane.
Sns and Kirre proteins localize to the ND at the entry point into the labyrinthine channels and, like their vertebrate counterparts, are essential for its formation.
GO:0016202 regulation of striated muscle tissue development
NAS PMID:20186342 The intracellular domain of Dumbfounded affects myoblast fus...
MODIFY
Summary: ComplexPortal NAS for the Sns adhesion complexes, citing a Dumbfounded intracellular-domain study. Sns participates directly in the recognition and adhesion step of myoblast fusion rather than regulating muscle tissue development.
Reason: Sns does part of the work of myoblast fusion (it is the fusion-competent-myoblast ligand of Duf/Kirre and Rst) and is not shown to modulate the rate or extent of striated muscle tissue development. The participation is best captured by GO:0007520 myoblast fusion, which the gene already carries with IMP support.
Duf/Rst expressed on the FC surface and SNS/Hbs expressed on the FCM surface are thought to bring about myoblast attraction, and have been suggested to actively participate in this process [9], [14], [18], [19].
The Drosophila sticks-and-stones (sns) locus was identified on the basis of its mutant phenotype, the complete absence of body wall muscles and corresponding presence of unfused myoblasts.
IDA PMID:26053791 The Cell Adhesion Molecules Roughest, Hibris, Kin of Irre an...
ACCEPT
Summary: Sns is localized in the apical contact region of sensory-organ precursor cells in the wing-disc analysis. This is consistent with its membrane-adhesion role, without implying universal apical localization in every tissue.
Reason: Sns is localized in the apical contact region of sensory-organ precursor cells in the wing-disc analysis. This is consistent with its membrane-adhesion role, without implying universal apical localization in every tissue.
IMP PMID:18003739 SCAR/WAVE and Arp2/3 are crucial for cytoskeletal remodeling...
KEEP AS NON CORE
Summary: Sns-mediated founder-cell adhesion is required for the dynamic F-actin focus that forms in fusion-competent myoblasts at the fusion site; in reconstituted S2R+ cell fusion, Sns-associated F-actin foci depend on WASP, WIP and SCAR.
Reason: The cached abstract of the cited study states that several known fusion components regulate the actin foci, without naming Sns, and its full text could not be retrieved. Independent reconstitution work summarized in the deep-research report links Sns to adaptor-mediated WASP/SCAR-Arp2/3 actin polymerization at the fusion interface, so Sns plausibly contributes to organizing this actin structure through its cytoplasmic tail. Deferring to the FlyBase IMP curator, the row is kept, but as non-core, because the actin polymerization itself is carried out by the WASP and SCAR/Arp2/3 machinery and Sns acts as the adhesion receptor that positions it.
Summary: ARBA-derived broad developmental process. True of Sns, but entailed by more specific experimentally supported process terms retained in this review.
Reason: The term is an ancestor of myoblast fusion (GO:0007520) and garland nephrocyte differentiation (GO:0061321), which are retained in this review with gene-specific IMP/IGI evidence, so it adds no information. The ARBA rule is not itself used as support.
The Drosophila sticks-and-stones (sns) locus was identified on the basis of its mutant phenotype, the complete absence of body wall muscles and corresponding presence of unfused myoblasts.
IMP PMID:18971929 The insect nephrocyte is a podocyte-like cell with a filtrat...
ACCEPT
Summary: Loss of Sns reduces or abolishes the nephrocyte diaphragm, demonstrating a direct structural adhesion contribution to assembly of the filtration junction.
Reason: Loss of Sns reduces or abolishes the nephrocyte diaphragm, demonstrating a direct structural adhesion contribution to assembly of the filtration junction.
Sns and Kirre proteins localize to the ND at the entry point into the labyrinthine channels and, like their vertebrate counterparts, are essential for its formation.
IMP PMID:19515699 Sns and Kirre, the Drosophila orthologs of Nephrin and Neph1...
ACCEPT
Summary: Loss of Sns reduces or abolishes the nephrocyte diaphragm, demonstrating a direct structural adhesion contribution to assembly of the filtration junction.
Reason: Loss of Sns reduces or abolishes the nephrocyte diaphragm, demonstrating a direct structural adhesion contribution to assembly of the filtration junction.
Sns and Kirre proteins localize to the ND at the entry point into the labyrinthine channels and, like their vertebrate counterparts, are essential for its formation.
Summary: The binding of Sns to Kirre/Roughest is supported by cell-recognition experiments and direct measurements of Drosophila heterocomplexes. This is a specific core molecular activity.
Reason: The binding of Sns to Kirre/Roughest is supported by cell-recognition experiments and direct measurements of Drosophila heterocomplexes. This is a specific core molecular activity.
IMP PMID:19515699 Sns and Kirre, the Drosophila orthologs of Nephrin and Neph1...
KEEP AS NON CORE
Summary: Sns mediates adhesion and fusion of garland nephrocytes into binucleate cells and supports their diaphragm formation. Retain the corresponding differentiation phenotype as a context-specific developmental consequence.
Reason: Sns mediates adhesion and fusion of garland nephrocytes into binucleate cells and supports their diaphragm formation. Retain the corresponding differentiation phenotype as a context-specific developmental consequence.
IMP PMID:18971929 The insect nephrocyte is a podocyte-like cell with a filtrat...
ACCEPT
Summary: Sns is an essential structural component of the nephrocyte filtration diaphragm; its depletion disrupts the junction and abolishes protein uptake. It participates in filtration without acting as an active solute pump.
Reason: Sns is an essential structural component of the nephrocyte filtration diaphragm; its depletion disrupts the junction and abolishes protein uptake. It participates in filtration without acting as an active solute pump.
Sns and Kirre proteins localize to the ND at the entry point into the labyrinthine channels and, like their vertebrate counterparts, are essential for its formation.
IMP PMID:23291470 An in vivo functional analysis system for renal gene discove...
ACCEPT
Summary: Sns is an essential structural component of the nephrocyte filtration diaphragm; its depletion disrupts the junction and abolishes protein uptake. It participates in filtration without acting as an active solute pump.
Reason: Sns is an essential structural component of the nephrocyte filtration diaphragm; its depletion disrupts the junction and abolishes protein uptake. It participates in filtration without acting as an active solute pump.
Sns and Kirre proteins localize to the ND at the entry point into the labyrinthine channels and, like their vertebrate counterparts, are essential for its formation.
Summary: Sns on fusion-competent myoblasts engages Kirre/Roughest on founder cells, directly supporting heterophilic recognition and adhesion. This adhesive mechanism also supports specialized nephrocyte contacts.
Reason: Sns on fusion-competent myoblasts engages Kirre/Roughest on founder cells, directly supporting heterophilic recognition and adhesion. This adhesive mechanism also supports specialized nephrocyte contacts.
Sns and Kirre proteins localize to the ND at the entry point into the labyrinthine channels and, like their vertebrate counterparts, are essential for its formation.
NAS PMID:19515699 Sns and Kirre, the Drosophila orthologs of Nephrin and Neph1...
ACCEPT
Summary: Sns on fusion-competent myoblasts engages Kirre/Roughest on founder cells, directly supporting heterophilic recognition and adhesion. This adhesive mechanism also supports specialized nephrocyte contacts.
Reason: Sns on fusion-competent myoblasts engages Kirre/Roughest on founder cells, directly supporting heterophilic recognition and adhesion. This adhesive mechanism also supports specialized nephrocyte contacts.
Sns and Kirre proteins localize to the ND at the entry point into the labyrinthine channels and, like their vertebrate counterparts, are essential for its formation.
IPI PMID:19270174 The immunoglobulin superfamily member Hbs functions redundan...
ACCEPT
Summary: Sns on fusion-competent myoblasts engages Kirre/Roughest on founder cells, directly supporting heterophilic recognition and adhesion. This adhesive mechanism also supports specialized nephrocyte contacts.
Reason: Sns on fusion-competent myoblasts engages Kirre/Roughest on founder cells, directly supporting heterophilic recognition and adhesion. This adhesive mechanism also supports specialized nephrocyte contacts.
Sns and Kirre proteins localize to the ND at the entry point into the labyrinthine channels and, like their vertebrate counterparts, are essential for its formation.
GO:0098636 protein complex involved in cell adhesion
IPI PMID:23827685 An extracellular interactome of immunoglobulin and LRR prote...
ACCEPT
Summary: The extracellular SnsβKirre/Roughest adhesion complex is physically supported by the interactome and independent heterocomplex affinity measurements. This provides a specific complex context for its cell-adhesion activity.
Reason: The extracellular SnsβKirre/Roughest adhesion complex is physically supported by the interactome and independent heterocomplex affinity measurements. This provides a specific complex context for its cell-adhesion activity.
theDrosophila homologs of SYG-1(Rst and Duf/Kirre) and of SYG-2(SNS and Hbs)all form hetero-complexes withaffinities between 1 to 4 ΞΌM
GO:0160108 animal gross anatomical part developmental process
IEA GO_REF:0000117
TOO GENERAL
Summary: ARBA-derived broad developmental process. True of Sns, but entailed by more specific experimentally supported process terms retained in this review.
Reason: The term is an ancestor of compound eye morphogenesis, chaeta morphogenesis, larval visceral muscle development and myoblast fusion, which are retained in this review with gene-specific IMP/IGI evidence, so it adds no information. The ARBA rule is not itself used as support.
The Drosophila sticks-and-stones (sns) locus was identified on the basis of its mutant phenotype, the complete absence of body wall muscles and corresponding presence of unfused myoblasts.
NAS PMID:11684662 Characterization of Drosophila hibris, a gene related to hum...
MODIFY
Summary: ComplexPortal NAS citing the Hibris characterization paper. Sns is an essential participant in myoblast fusion (unfused myoblasts in sns mutants), acting as the FCM ligand for Kirre/Rst, not a regulator modulating fusion frequency or rate.
Reason: The evidence supports direct participation in myoblast fusion rather than regulation of it, so the row is redirected to GO:0007520 myoblast fusion, which the gene already carries with IMP support. Sns's cytoplasmic domain contributing to precursor formation is part of its fusion-mediating role, not a separate regulatory activity.
The Drosophila sticks-and-stones (sns) locus was identified on the basis of its mutant phenotype, the complete absence of body wall muscles and corresponding presence of unfused myoblasts.
The Drosophila sticks-and-stones (sns) locus was identified on the basis of its mutant phenotype, the complete absence of body wall muscles and corresponding presence of unfused myoblasts.
Sns and Kirre proteins localize to the ND at the entry point into the labyrinthine channels and, like their vertebrate counterparts, are essential for its formation.
Q: Does the 63-residue insertion unique to isoform B (Q0E9F2 residues 1060-1122), which carries a second predicted transmembrane segment, actually span the membrane, and if so does it invert or sequester the cytoplasmic tail that recruits fusion machinery?
Q: Is the garland-nephrocyte adhesion requirement (curated as homophilic cell-cell adhesion) mediated by Sns-Sns trans binding, or by heterophilic Sns-Kirre binding between co-expressing cells?
Q: Does the Sns cytoplasmic domain directly organize the F-actin focus in fusion-competent myoblasts, or is actin focus formation only a downstream consequence of Sns-mediated founder-cell adhesion?
Suggested Experiments
Experiment: Express tagged isoforms A and B in S2 cells or FCMs and map tail orientation by selective permeabilization or protease protection; test each isoform for rescue of sns myoblast fusion and nephrocyte diaphragm defects.
Hypothesis: The isoform-B-specific hydrophobic insertion is a functional transmembrane segment.
Experiment: Cell-aggregation and surface-plasmon-resonance assays with Sns ectodomain alone versus Sns plus Kirre, alongside GCN adhesion assays in kirre-null backgrounds expressing Sns.
Hypothesis: Sns does not bind itself in trans.
External Prediction Reviews
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Q0E9F2 is the representative GOA product of the Drosophila sns gene, a nephrin-subfamily transmembrane immunoglobulin-superfamily adhesion receptor required for myoblast fusion, garland nephrocyte adhesion and fusion, nephrocyte diaphragm formation and ommatidial patterning. All three ProtNLM2 terms (cell differentiation, anatomical structure morphogenesis, membrane) are true of the gene but are ancestors of more specific terms it already carries with experimental support (garland nephrocyte differentiation and myoblast fusion; compound eye and chaeta morphogenesis; plasma membrane and nephrocyte diaphragm), and each exact term is already in GOA for this accession. They are therefore scored as less precise than existing annotation. The 63-residue insertion specific to this isoform (with a predicted extra hydrophobic segment) is an open topology question but does not refute these broad gene-level terms.
Review rationale: Sns is required for myoblast fusion in body-wall muscle formation and for adhesion and fusion of garland nephrocytes into binucleate cells. Both myoblast fusion (GO:0007520) and garland nephrocyte differentiation (GO:0061321) are is_a descendants of cell differentiation (checked in OLS4) and are carried by the gene with IMP evidence; the exact term is also already in GOA for this accession. The prediction is correct but less precise than existing supported annotation.
Supporting Evidence:
PMID:10859168: "The Drosophila sticks-and-stones (sns) locus was identified on the basis of its mutant phenotype, the complete absence of body wall muscles and corresponding presence of unfused myoblasts."
PMID:19515699: "contribute to adhesion of GCNs in the ;garland' and to their fusion into binucleate cells"
Review rationale: Sns-mediated preferential adhesion maintains ommatidial separation in the developing eye, and Sns contributes to spacing of sensory bristles. The gene carries compound eye morphogenesis (GO:0001745, IMP) and chaeta morphogenesis (GO:0008407, IGI), both descendants of anatomical structure morphogenesis (checked in OLS4); the exact term is also already in GOA for this accession. The prediction is correct but less precise than existing supported annotation.
Supporting Evidence:
PMID:20599904: "These results strongly suggest expression of Hbs and Sns is sufficient to render ommatidia less adhesive to other ommatidia than to IOCs."
Review rationale: Sns is a transmembrane cell-surface adhesion receptor that is enriched at the membrane at myoblast fusion sites and localizes to the nephrocyte plasma membrane and nephrocyte diaphragm. The gene carries plasma membrane (GO:0005886, IDA and IBA), an is_a descendant of membrane (checked in OLS4), and nephrocyte diaphragm (IDA). The isoform-specific extra hydrophobic segment does not undermine membrane association. The prediction is correct but less precise than existing supported annotation.
Supporting Evidence:
PMID:10859168: "SNS is enriched at the membrane and clusters at discrete sites, coincident with the occurrence of myoblast fusion."
PMID:18971929: "Both proteins localise to the plasma membrane (Fig. 2d-g) and double labelling reveals precise co-localisation (Fig. 2h)."
file:DROME/sns/sns-bioinformatics/RESULTS.md: "The selected record predicts transmembrane segments 1089β1112 (within the insertion) and 1141β1166 (in the shared sequence)."
sticks and stones (sns) encodes a single-pass transmembrane protein of the immunoglobulin superfamily, which mediates cell-cell recognition and adhesion. The product of sns marks the fusion competent population of myoblasts. It also contributes to formation and function of the nephrocyte diaphragm and cell sorting within the developing ommatidia.