Cell Density Sensing
Figure 1. The cartoon above indicates a tissue containing two different cell types, indicated by the blue and green ovals. How can a tissue sense the percent of the cells indicated in green to regulate its composition? If the green cells secrete a characteristic factor, the concentration of the factor in the tissue will be a function of the percent of green cells in the tissue. We found a paradigm for this sort of factor in Dictyostelium – when cells overgrow their food supply and starve, some cells starve while other cells are still finding and eating food. To let the population know how many cells are starving, the starved cells secrete a characteristic factor called CMF, and we elucidated the CMF diffusion physics and signal transduction pathway.
Figure 2. When Dictyostelium cells starve, they begin secreting a glycoprotein called conditioned medium factor (CMF). When there is a high density of starved cells, as indicated by a high concentration of CMF, the cells begin expressing some of the genes involved in development and aggregate using pulses of cAMP as a chemoattractant. CMF regulates gene expression via a G protein-independent pathway, and simultaneously regulates cAMP signal transduction via a G protein-dependent pathway.
Key Papers
Deery, W.J., Gao, T., Ammann, R.A., and Gomer, R.H. A single cell-density sensing factor stimulates distinct signal transduction pathways through two different receptors. J. Biol. Chem. 277, 31972-31979 (2002).
Deery, W.J. and Gomer, R.H. A putative receptor mediating cell-density sensing in Dictyostelium. J. Biol. Chem. 274, 34476-34482 (1999).
Brazill, D.T., Lindsey, D.F., Bishop, J.D., and Gomer, R.H. Cell-density sensing mediated by a G-protein-coupled receptor activating phospholipase C. J. Biol. Chem. 273, 8161-8168 (1998).
Brazill, D.T., Gundersen, R. and Gomer, R.H. A cell-density sensing factor regulates the lifetime of a chemoattractant-induced Ga-GTP conformation. FEBS Letters 404, 100-104. (1997).
Van Haastert, P.J.M., Bishop, J.D., and Gomer, R.H. The cell density factor CMF regulates the chemoattractant receptor cAR1 in Dictyostelium. J. Cell Biol. 134, 1543-1549 (1996).
Clarke, M. and Gomer, R.H. PSF and CMF, autocrine factors that regulate gene expression during growth and early development of Dictyostelium. Experientia 51, 1124-1134 (1995).
Yuen, I.S., Jain, R., Bishop, J.D., Lindsey, D.F., Deery, W.J., Van Haastert, P.J.M., and Gomer, R.H. A density-sensing factor regulates signal transduction in Dictyostelium. J. Cell Biol. 129, 1251-1262 (1995).
Jain, R., and Gomer, R.H. A developmentally regulated cell surface receptor for a density-sensing factor in Dictyostelium. J. Biol. Chem. 269, 9128-9136 (1994).
Yuen, I.S., and Gomer, R.H. Cell density-sensing in Dictyostelium by means of the accumulation rate, diffusion coefficient and activity threshold of a protein secreted by starved cells. J. Theoretical Biology 167, 273-282 (1994).
Jain, R., Yuen, I.S., Taphouse, C.R., and Gomer, R.H. A density sensing factor controls development in Dictyostelium. Genes & Development 6, 390-400 (1992).
Clarke, M., Dominguez, N., Yuen, I.S., and Gomer, R.H. Growing and starving Dictyostelium cells produce distinct density-sensing factors. Dev. Biol. 152, 403-406 (1992).
Gomer, R.H., Yuen, I.S., and Firtel, R.A. A secreted 80×103 Mr protein mediates sensing of cell density and the onset of development in Dictyostelium. Development 112, 269-278 (1991).
Yuen, I.S., Taphouse, C., Halfant, K., and Gomer, R.H. Regulation and processing of a secreted protein that mediates sensing of cell density in Dictyostelium. Development 113, 1375-1385 (1991).