Guanine nucleotides modulate the ligand binding properties of cell surface folate receptors in Dictyostelium discoideum.
Dictyostelium discoideum cells show 2 distinct classes of cell surface binding sites for folates. One type is non-specific, i.e., binds folic acid (FA), 2-deaminofolic acid (DAFA), and methotrexate (MTX) with similar affinity (K0.5 congruent to 140 nM). Scatchard analysis of this non-specific binding type suggests either heterogeneity or negative cooperativity. Isolated D. discoideum membranes show similar binding characteristics. Guanine nucleotides changed the binding levels of [3H]MTX. In the presence of 0.1 mM GTP, the number of binding sites remains unchanged, while the affinity decreases. GDP and guanylyl imidodiphosphate (GPPNP) are required at about 20-fold higher concentration than GTP, which elicits a half-maximal effect at 15 microM. Other guanine and adenine nucleotides are ineffective up to 1 mM. These results suggests that the non-specific cell surface receptor for folic acid interacts with a guanine nucleotide regulatory (G-) protein.
D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004023:Dictyostelium / Q000378:metabolism*; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006153:Guanosine Diphosphate / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007700:Kinetics; D008727:Methotrexate / Q000378:metabolism; D011956:Receptors, Cell Surface
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D006150:Guanine Nucleotides; D011956:Receptors, Cell Surface; D006153:Guanosine Diphosphate; C044134:2-deaminofolic acid; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D005492:Folic Acid; D008727:Methotrexate