Contact site A protein (csA, also known as gp80) is a developmentally regulated, glycolipid-anchored cell-surface glycoprotein of the social amoeba Dictyostelium discoideum. Its expression is restricted to the aggregation stage of development and is induced by pulsatile cAMP signaling acting through cell-surface cAMP receptors. csA mediates EDTA-resistant (Ca2+-independent) cell-cell adhesion through homophilic binding, in which csA molecules on one cell surface bind directly to csA molecules on adjacent cells. The mature protein carries N-linked glycans and is attached to the outer face of the plasma membrane by an unusual phosphoceramide-containing (GPI-like) lipid anchor. csA is enriched at cell-cell contact regions and on filopodia, where it partitions into sterol-rich, detergent-resistant membrane microdomains and colocalizes with the underlying cortical actin cytoskeleton. It provides a fast, shear-resistant form of intercellular cohesion during the transition from unicellular amoebae to a multicellular aggregate; loss of csA abolishes EDTA-stable adhesion, and under natural or semi-natural conditions csA-null cells show reduced cell-cell cohesion, increased substratum adhesion, slower motility, and a competitive disadvantage, whereas strong overexpression perturbs morphogenesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: csA is a plasma membrane-associated glycoprotein, attached to the outer face of the membrane by a GPI-like lipid anchor. Plasma membrane localization is correct and consistent with direct experimental evidence. Reason: csA is a bona fide plasma membrane protein. The UniProt subcellular location mapping is corroborated by direct evidence that gp80 is a lipid-anchored membrane component enriched at the cell surface. Supporting Evidence: PMID:11278598 the phospholipid-anchored cell adhesion molecule gp80 |
| GO:0007156 homophilic cell-cell adhesion | IDA PMID:3320049 The contact site A glycoprotein mediates cell-cell adhesion ... | ACCEPT | Summary: Direct binding assays (gp80-coated Covaspheres, filter-binding, and inhibition of cell reassociation by soluble gp80) demonstrate that csA/gp80 mediates cell-cell binding via homophilic interaction. This is the core function of the gene product. Reason: This is the defining, experimentally demonstrated function of csA - homophilic cell-cell adhesion at the aggregation stage. Supporting Evidence: PMID:3320049 gp80 mediates cell-cell binding at the aggregation stage of development via homophilic interaction |
| GO:0016338 calcium-independent cell-cell adhesion | IMP PMID:2515990 Selective elimination of the contact site A protein of Dicty... | ACCEPT | Summary: Gene disruption of csA drastically reduced EDTA-stable (Ca2+-independent) adhesion, directly confirming that csA is responsible for the calcium-independent form of cell-cell adhesion in aggregating cells. Reason: Loss-of-function evidence establishes csA as the mediator of EDTA-stable, Ca2+-independent adhesion; this is a core aspect of its function. Supporting Evidence: PMID:2515990 This protein has been implicated in the EDTA-stable (Ca2(+)-independent) type of cell adhesion of aggregating cells PMID:2515990 EDTA-stable adhesion was drastically reduced as compared to wild type, confirming that the contact site A glycoprotein acts as a cell-adhesion molecule |
| GO:0098632 cell-cell adhesion mediator activity | IDA PMID:3320049 The contact site A glycoprotein mediates cell-cell adhesion ... | ACCEPT | Summary: Purified gp80 conjugated to beads binds cells in a developmentally regulated, antibody-blockable manner, showing that gp80 participates directly in cell binding. This is the core molecular function. Reason: Direct binding evidence supports cell-cell adhesion mediator activity as the core molecular function of csA. Supporting Evidence: PMID:3320049 gp80 participates directly in cell binding |
| GO:0009897 external side of plasma membrane | IDA PMID:6191197 Monoclonal antibody recognizing gp80, a membrane glycoprotei... | ACCEPT | Summary: csA/gp80 is displayed on the external face of the plasma membrane via its lipid anchor, where it engages in intercellular adhesion. This localization is consistent with its function as a surface adhesion molecule. Reason: csA is an outer-leaflet, lipid-anchored surface glycoprotein; the external side of the plasma membrane is where its adhesive activity operates. Supporting Evidence: PMID:6191197 gp80, a membrane glycoprotein implicated in intercellular adhesion of Dictyostelium discoideum |
| GO:0009986 cell surface | TAS PMID:15366765 Comparison of molecular mechanisms mediating cell contact ph... | ACCEPT | Summary: csA/gp80 is a developmentally regulated cell-surface glycoprotein. The cell-surface localization is well established from multiple primary studies. Reason: Cell-surface localization is a correct and well-supported location for this GPI-anchored adhesion glycoprotein. Supporting Evidence: PMID:3320049 developmentally regulated cell surface glycoprotein of Mr 80,000 (gp80) |
| GO:0005911 cell-cell junction | IDA PMID:11278598 Involvement of a triton-insoluble floating fraction in Dicty... | ACCEPT | Summary: gp80 colocalizes with F-actin, porin, and comitin at cell-cell contacts during development, consistent with its adhesive activity operating at cell-cell junction/contact regions. Reason: Direct evidence places csA at cell-cell contact regions where it mediates adhesion. Supporting Evidence: PMID:11278598 gp80 colocalized with F-actin, porin, and comitin at cell-cell contacts |
| GO:0005911 cell-cell junction | IDA PMID:8806827 Novel redistribution of the Ca(2+)-dependent cell adhesion m... | ACCEPT | Summary: gp80 becomes concentrated in contact regions among cells within well-developed streams during aggregation, supporting its localization to cell-cell junctions/contact sites. Reason: Independent evidence confirms csA enrichment at cell-cell contact regions during aggregation. Supporting Evidence: PMID:8806827 gp80 is concentrated in contact regions among cells within well-developed streams |
| GO:0045121 membrane raft | TAS PMID:15366765 Comparison of molecular mechanisms mediating cell contact ph... | ACCEPT | Summary: csA/gp80 partitions into a sterol-enriched, Triton-insoluble floating fraction (a lipid raft-like microdomain), consistent with membrane raft localization of this lipid-anchored protein. Reason: gp80 associates with detergent-resistant, sterol-rich membrane microdomains, supporting membrane raft localization. Supporting Evidence: PMID:11278598 confirmed the association of gp80 and comitin with TIFF membranes PMID:11278598 the sterol/phospholipid ratio of TIFF was 10-fold higher than that of the bulk plasma membrane |
| GO:0098609 cell-cell adhesion | IDA PMID:3934167 Inhibition of cell-cell binding at the aggregation stage of ... | ACCEPT | Summary: Class I anti-gp80 monoclonal antibodies block EDTA-resistant contact sites and inhibit cell reassociation at the aggregation stage, consistent with a direct role of gp80 in cell-cell binding. Reason: Antibody-blocking evidence supports the general cell-cell adhesion role; this is a core function (more specifically captured as homophilic, Ca2+-independent adhesion). Supporting Evidence: PMID:3934167 consistent with a direct role of gp80 in cell-cell binding |
| GO:0042802 identical protein binding | IPI PMID:8660574 Oriented binding of a lipid-anchored cell adhesion protein o... | ACCEPT | Summary: Biosensor experiments show that immobilized csA interacts with csA in solution, establishing that csA molecules engage in homophilic (self) binding. This identical protein binding is the molecular basis of csA-mediated adhesion, and is more informative than bare protein binding. Reason: The homophilic self-interaction (identical protein binding) is the mechanistic basis of csA adhesion and is directly demonstrated in vitro. Supporting Evidence: PMID:8660574 Interaction of the immobilized csA protein with csA in solution established that the bound molecules are capable of taking part in homophilic interactions |
| GO:0010225 response to UV-C | IDA PMID:25858552 Response of Dictyostelium discoideum to UV-C and involvement... | MARK AS OVER ANNOTATED | Summary: This study reports that csA mRNA expression is markedly reduced following UV-C irradiation of Dictyostelium cells. csA is used here as a developmentally regulated readout of UV-C-induced developmental impairment, not as a functional effector of the UV-C response. There is no evidence that csA acts within a UV-C damage-response pathway. Reason: The evidence is a change in csA transcript level after UV-C exposure, which reflects downstream disruption of the aggregation program rather than a role for csA in responding to UV-C. Annotating csA as acting upstream of or within the UV-C response over-interprets an expression readout. Supporting Evidence: PMID:25858552 expression of csA and ctnA was markedly reduced |
| GO:0030175 filopodium | IDA PMID:3553212 Filopodia are enriched in a cell cohesion molecule of Mr 80,... | ACCEPT | Summary: Immunoelectron microscopy shows gp80 preferentially localized on filopodia (about twofold higher gold density) in addition to contact regions, where filopodia participate in initial cell-cell contact formation. Reason: Direct localization evidence places csA on filopodia, a genuine (though not sole) site of the adhesion protein. Supporting Evidence: PMID:3553212 gold particles were found preferentially localized on filopodia |
| GO:0005886 plasma membrane | IDA PMID:3934167 Inhibition of cell-cell binding at the aggregation stage of ... | ACCEPT | Summary: gp80 is characterized as an 80,000-dalton surface/membrane glycoprotein, supporting direct-evidence plasma membrane localization. Reason: Plasma membrane localization is directly supported; consistent with the IEA subcellular-location annotation. Supporting Evidence: PMID:3934167 a surface glycoprotein with an apparent Mr of 80,000 (gp80) |
| GO:1904643 response to curcumin | IDA PMID:26449461 Curcumin inhibits development and cell adhesion in Dictyoste... | MARK AS OVER ANNOTATED | Summary: Curcumin treatment suppresses expression of cell adhesion proteins including csA, with consequent delays in adhesion and development. csA is a developmentally regulated readout affected by curcumin, not a mediator of the curcumin response. Reason: The evidence is downregulation of csA expression by curcumin (an effect on the aggregation program), not a function of csA in responding to curcumin. Annotating csA as involved in the curcumin response over-interprets an expression change. Supporting Evidence: PMID:26449461 expression of the extracellular matrix/cell adhesion proteins (DdCAD and csA) |
| GO:0031152 aggregation involved in sorocarp development | IMP PMID:1328260 Overexpression of the csA cell adhesion molecule under its o... | ACCEPT | Summary: Strong overexpression of csA under its own cAMP-regulated promoter delays aggregation and substantially alters morphogenesis, linking csA levels to the aggregation phase of sorocarp (fruiting body) development. Reason: Perturbation of csA expression alters aggregation and morphogenesis, supporting a role in aggregation during sorocarp development. Supporting Evidence: PMID:1328260 When the csA protein was strongly overexpressed under the developmental control of the csA promoter, morphogenesis was substantially altered PMID:1328260 Aggregation was delayed |
| GO:0031152 aggregation involved in sorocarp development | IEP PMID:25887420 Leaps and lulls in the developmental transcriptome of Dictyo... | ACCEPT | Summary: csaA is expressed as a cell-cell adhesion gene during aggregation, with induction kinetics tied to pulsatile cAMP, consistent with its role in the aggregation phase. This is expression-pattern (IEP) evidence supporting the same process captured by stronger mutant evidence. Reason: The expression-pattern evidence corroborates csA involvement in the aggregation phase of sorocarp development, consistent with the gain- and loss-of-function evidence for the same process. Supporting Evidence: PMID:25887420 several of its putative target genes involved in aggregation (such as the cell-cell adhesion gene csaA) |
| GO:0030587 sorocarp development | IMP PMID:9689085 Detection of subtle phenotypes: the case of the cell adhesio... | ACCEPT | Summary: Under semi-natural (soil) conditions, csA-null cells display reduced cell-cell adhesion, increased substratum adhesion, and slower motility, and csA is required for efficient development, demonstrating a role in sorocarp development beyond the mild laboratory phenotype. Reason: Sensitive assays reveal that csA is required for efficient development, supporting its role in sorocarp development. Supporting Evidence: PMID:9689085 evidence is provided that csA is required for development |
| GO:0098609 cell-cell adhesion | IMP PMID:6191197 Monoclonal antibody recognizing gp80, a membrane glycoprotei... | ACCEPT | Summary: gp80 is implicated in the EDTA-resistant intercellular adhesions (contact sites A) that appear during development, and it carries the determinants associated with adhesion. This supports a role in cell-cell adhesion, consistent with the broader body of evidence. Reason: csA/gp80 is implicated in intercellular adhesion; cell-cell adhesion is a core biological process for this gene. Supporting Evidence: PMID:6191197 gp80 has been implicated in the formation of the EDTA-resistant adhesions |
| GO:0030866 cortical actin cytoskeleton organization | TAS PMID:15366765 Comparison of molecular mechanisms mediating cell contact ph... | KEEP AS NON CORE | Summary: csA/gp80 colocalizes with F-actin at cell-cell contacts and recruits F-actin and associated proteins into gp80 caps, linking csA-mediated adhesion to the underlying cortical actin cytoskeleton. This is a secondary, adhesion-associated role rather than the core adhesion function itself. Reason: There is evidence that csA-based contacts organize/recruit cortical actin, but this is a downstream consequence of adhesion rather than the core molecular function of csA. Supporting Evidence: PMID:11278598 These proteins were also recruited to gp80 caps induced by antibody cross-linking |
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