A secreted cell number counting factor represses intracellular glucose levels to regulate group size in dictyostelium.
Developing Dictyostelium cells form evenly sized groups of approximately 2 x 10(4) cells. A secreted 450-kDa protein complex called counting factor (CF) regulates group size by repressing cell-cell adhesion and myosin polymerization and by increasing cAMP-stimulated cAMP production, actin polymerization, and cell motility. We find that CF regulates group size in part by repressing internal glucose levels. Transformants lacking bioactive CF and wild-type cells with extracellular CF depleted by antibodies have high glucose levels, whereas transformants oversecreting CF have low glucose levels. A component of CF, countin, affects group size in a manner similar to CF, and a 1-min exposure of cells to countin decreases glucose levels. Adding 1 mm exogenous glucose negates the effect of high levels of extracellular CF on group size and mimics the effect of depleting CF on glucose levels, cell-cell adhesion, cAMP pulse size, actin polymerization, myosin assembly, and motility. These results suggest that glucose is a downstream component in part of the CF signaling pathway and may be relevant to the observed role of the insulin pathway in tissue size regulation in higher eukaryotes.
Jang
Wonhee
W
Howard Hughes Medical Institute and the Department of Biochemistry and Cell Biology, Rice University, Houston, Texas 77005-1892, USA.
Chiem
Binh
B
Gomer
Richard H
RH
D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D003198:Computer Simulation; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004023:Dictyostelium / Q000378:metabolism / Q000502:physiology*; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D009218:Myosins / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
D015800:Protozoan Proteins; D011994:Recombinant Proteins; C120918:countin protein, Dictyostelium discoideum; D000242:Cyclic AMP; D009218:Myosins; D006152:Cyclic GMP; D005947:Glucose