A single cell density-sensing factor stimulates distinct signal transduction pathways through two different receptors.
In Dictyostelium discoideum, cell density is monitored by levels of a secreted protein, conditioned medium factor (CMF). CMFR1 is a putative CMF receptor necessary for CMF-induced G protein-independent accumulation of the SP70 prespore protein but not for CMF-induced G protein-dependent inositol 1,4,5-trisphosphate production. Using recombinant fragments of CMF, we find that stimulation of the inositol 1,4,5-trisphosphate pathway requires amino acids 170-180, whereas SP70 accumulation does not, corroborating a two-receptor model. Cells lacking CMFR1 do not aggregate, due to the lack of expression of several important early developmentally regulated genes, including gp80. Although many aspects of early developmental cAMP-stimulated signal transduction are mediated by CMF, CMFR1 is not essential for cAMP-stimulated cAMP and cGMP production or Ca(2+) uptake, suggesting the involvement of a second CMF receptor. Exogenous application of antibodies against either the region between a first and second or a second and third possible transmembrane domain of CMFR1 induces SP70 accumulation. Antibody- and CMF-induced gene expression can be inhibited by recombinant CMFR1 corresponding to the region between the first and third potential transmembrane domains, indicating that this region is extracellular and probably contains the CMF binding site. These observations support a model where a one- or two-transmembrane CMFR1 regulates gene expression and a G protein-coupled CMF receptor mediates cAR1 signal transduction.
Deery
William J
WJ
Howard Hughes Medical Institute, Department of Biochemistry and Cell Biology, Rice University, Houston, Texas 77005-1892, USA.
Gao
Tong
T
Ammann
Robin
R
Gomer
Richard H
RH
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers; D004023:Dictyostelium / Q000166:cytology / Q000502:physiology*; D008934:Mitogens / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D011506:Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D017931:DNA Primers; D008934:Mitogens; D011506:Proteins; D011994:Recombinant Proteins; C119500:coelomic mitogenic factor, 60-kDa