cmfA encodes conditioned medium factor (CMF), a secreted ~80-kDa N- and O-glycosylated protein that functions as a cell-density (quorum) sensing signal during the transition from growth to multicellular development in Dictyostelium discoideum. When cells starve they slowly secrete CMF, and the extracellular concentration of CMF therefore reports the local density of starving cells. Starving cells must accumulate CMF above a threshold before they become competent to respond to pulsatile cAMP and initiate chemotactic aggregation; below this threshold cells do not express early developmental genes or differentiate into prespore and prestalk cells in response to cAMP. CMF acts as a ligand for cell-surface receptors (including CMFR1), and its signal is transduced in part through a heterotrimeric G protein that couples density sensing to the cAMP chemoattractant receptor cAR1, while a G protein-independent branch controls gene expression. Through this mechanism CMF couples cell density to the timing of developmental onset, synchronizing aggregation once a majority of cells in an area have starved.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0031152 aggregation involved in sorocarp development | IMP PMID:1547939 A density-sensing factor controls development in Dictyosteli... | ACCEPT | Summary: CMF is required for chemotactic aggregation during the growth-to- development transition. Antisense knockdown of CMF blocks aggregation, and exogenous purified CMF restores normal development, providing strong loss-of-function and rescue evidence that CMF acts upstream of aggregation. This captures a core biological role of the gene. Reason: Directly supported by IMP evidence (antisense transformants plus protein-rescue) from the cloning paper. CMF is a bona fide upstream regulator of aggregation, so the term and qualifier are appropriate. Supporting Evidence: PMID:1547939 CMF antisense transformants do not aggregate, whereas normal development is restored by the addition of purified CMF protein PMID:1547939 CMF might synchronize the onset of development in Dictyostelium by triggering aggregation when a majority of the cells in a given area have starved |
| GO:0005576 extracellular region | IDA PMID:1663029 A secreted 80 x 10(3) Mr protein mediates sensing of cell de... | ACCEPT | Summary: CMF is a secreted protein that acts in the extracellular medium as a diffusible density indicator. It was purified as an ~80-kDa protein from conditioned medium, consistent with an extracellular localization. The annotation is correct and reflects where the protein acts. Reason: Direct biochemical evidence shows CMF is a secreted extracellular factor purified from conditioned medium; the located_in extracellular region annotation is well supported. UniProt/dictyBase also record the more specific extracellular space (GO:0005615), but the extracellular region annotation is not wrong. Supporting Evidence: PMID:1663029 CMF is a secreted factor that functions in vivo as an indicator of cell density in starved cells PMID:1663029 can be purified to a single 80 x 10(3) Mr band on a silver-stained SDS-polyacrylamide gel |
| GO:0010468 regulation of gene expression | IDA PMID:1663029 A secreted 80 x 10(3) Mr protein mediates sensing of cell de... | ACCEPT | Summary: CMF is required for the density-dependent induction of early developmental gene expression. Below a threshold CMF concentration, starving cells fail to initiate expression of genes required for early development and do not acquire competence to induce prestalk/prespore genes in response to cAMP. The term is correct but general; the more specific developmental differentiation role is captured by GO:0045597. Reason: Directly supported by IDA evidence that CMF is needed for early developmental gene expression. The term is fairly high-level but accurate for this signaling factor, which controls the developmental gene-expression program. Supporting Evidence: PMID:1663029 When present below a threshold concentration, cells do not initiate the expression of genes required for early development PMID:1663029 This factor plays an essential role in the regulatory pathway necessary for cells to obtain the developmental competence to induce prestalk and prespore gene expression in response to cAMP |
| GO:0045597 positive regulation of cell differentiation | IDA PMID:1663029 A secreted 80 x 10(3) Mr protein mediates sensing of cell de... | ACCEPT | Summary: CMF positively regulates differentiation into prespore and prestalk cells. At high cell density (high CMF), cells differentiate in response to cAMP; conditioned medium (containing CMF) allows low-density cells to differentiate, and sufficient CMF enables cells to enter the multicellular stage. This is a core role of CMF and is well supported. Reason: Directly supported by IDA evidence that CMF is required for and promotes prespore/prestalk differentiation. Appropriate specific term for this developmental signaling factor. Supporting Evidence: PMID:1663029 At high cell densities, the concentration of CMF is sufficient to enable cells to enter the multicellular stage of the developmental cycle PMID:1663029 necessary for cells to obtain the developmental competence to induce prestalk and prespore gene expression in response to cAMP |
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