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Modeling Yeast Cell Polarization Induced by Pheromone Gradients

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Abstract

Yeast cells respond to spatial gradients of mating pheromones by polarizing and projecting up the gradient toward the source. It is thought that they employ a spatial sensing mechanism in which the cell compares the concentration of pheromone at different points on the cell surface and determines the maximum point, where the projection forms. Here we constructed the first spatial mathematical model of the yeast pheromone response that describes the dynamics of the heterotrimeric and Cdc42p G-protein cycles, which are linked in a cascade. Two key performance objectives of this system are (1) amplification—converting a shallow external gradient of ligand to a steep internal gradient of protein components and (2) tracking—following changes in gradient direction. We used simulations to investigate amplification mechanisms that allow tracking. We identified specific strategies for regulating the spatial dynamics of the protein components (i.e. their changing location in the cell) that would enable the cell to achieve both objectives.

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References

  1. D. G. Drubin and W. J. Nelson, Origins of cell polarity. Cell 84:335–344 (1996).

    Google Scholar 

  2. A. G. Gilman, et al., Overview of the alliance for cellular signaling. Nature 420:703–706 (2002).

    Google Scholar 

  3. G. F. Sprague Jr. and J. W. Thorner, in The Molecular and Cellular Biology of the Yeast Saccharomyces: Gene Expression (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 1992).

  4. H. G. Dohlman and J. W. Thorner, Regulation of G protein-initiated signal transduction in yeast: Paradigms and principles. Annu. Rev. Biochem. 70:703–754 (2001).

    Google Scholar 

  5. D. Pruyne and A. Bretscher, Polarization of cell growth in yeast: I. Establishment and maintenance of polarity states. J. Cell Sci. 113:365–375 (2000).

    Google Scholar 

  6. C. L. Jackson, J. B. Konopka and L. H. Hartwell, S. cerevisiae alpha pheromone receptors activate a novel signal transduction pathway for mating partner discrimination. Cell 67:389–402 (1991).

    Google Scholar 

  7. N. Hao, N. Yildirim, Y. Wang, T. C. Elson and H. G. Dohlman, Regulators of G protein signaling and transient activation of signaling: Experimental and computational analysis reveals negative and positive feedback controls on G protein activity. J. Biol. Chem. 278:46506–46515 (2003).

    Google Scholar 

  8. B. Kofahl and E. Klipp, Modelling the dynamics of the yeast pheromone pathway. Yeast 21:831–850 (2004).

    Google Scholar 

  9. T.-M. Yi, H. Kitano and M. I. Simon, A quantitative characterization of the yeast heterotrimeric G protein cycle. Proc. Natl. Acad. Sci. USA 100:10764–10769 (2003).

    Google Scholar 

  10. S. Sivakumaran, S. Hariharaputran, J. Mishra and U. S. Bhalla, The database of quantitative cellular signaling: Management and analysis of chemical kinetic models of signaling networks. Bioinformatics 19:408–415 (2003).

    Google Scholar 

  11. A. C. Butty, N. Perrinjaquet, A. Petit, M. Jaquenoud, J. E. Segall, K. Hofmann, C. Swahlen and M. Peter, A positive feedback loop stabilizes the guanine-nucleotide exchange factor Cdc24 at sites of polarization. EMBO J. 21:1565–1576 (2002).

    Google Scholar 

  12. J. E. Segall, Polarization of yeast cells in spatial gradients of alpha mating factor. Proc. Natl. Acad. Sci. USA 90:8332–8336 (1993).

    Google Scholar 

  13. D. Angeli, J. E. Ferrell, Jr. and E. D. Sontag, Detection of multistability, bifurcations, and hysteresis in a large class of biological positive-feedback systems. Proc. Natl. Acad. Sci. USA 101:1822–1827 (2004).

    Google Scholar 

  14. K. Jacobson, A. Ishihara and R. Inman, Lateral diffusion of proteins in membranes. Annu. Rev. Physiol. 49:163–175 (1987).

    Google Scholar 

  15. K. Suzuki, K. Ritchie, E. Kajikawa, T. Fujiwara and A. Kusumi, Rapid hop diffusion of a G-protein-coupled receptor in the plasma membrane as revealed by single-molecule techniques. Biophys. J. 88:3659–3680 (2005).

    Google Scholar 

  16. F. R. Maxfield, Plasma membrane microdomains. Curr. Opin. Cell Biol. 14:483–487 (2002).

    Google Scholar 

  17. J. Dobbelaere and Y. Barral, Spatial coordination of cytokinetic events by compartmentalization of the cell cortex. Science 305:393–396 (2004).

    Google Scholar 

  18. A. Nern and R. A. Arkowitz, G proteins mediate changes in cell shape by stabilizing the axis of polarity. Mol. Cell 5:853–864 (2000).

    Google Scholar 

  19. P. Devreotes and C. Janetopoulos, Eukaryotic chemotaxis: Distinctions between directional sensing and polarization. J. Biol. Chem. 278:20445–20448 (2003).

    Google Scholar 

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Correspondence to Tau-Mu Yi.

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Yi, TM., Chen, S., Chou, CS. et al. Modeling Yeast Cell Polarization Induced by Pheromone Gradients. J Stat Phys 128, 193–207 (2007). https://doi.org/10.1007/s10955-007-9285-1

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  • DOI: https://doi.org/10.1007/s10955-007-9285-1

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