Tracking Shallow Chemical Gradients by Actin-Driven Wandering of the Polarization Site

BACKGROUND Many cells are remarkably proficient at tracking very shallow chemical gradients, despite considerable noise from stochastic receptor-ligand interactions. Motile cells appear to undergo a biased random walk: spatial noise in receptor activity may determine the instantaneous direction, but because noise is spatially unbiased, it is filtered out by time averaging, resulting in net movement upgradient. How nonmotile cells might filter out noise is unknown. RESULTS Using yeast chemotropic mating as a model, we demonstrate that a polarized patch of polarity regulators "wanders" along the cortex during gradient tracking. Computational and experimental findings suggest that actin-directed membrane traffic contributes to wandering by diluting local polarity factors. The pheromone gradient appears to bias wandering via interactions between receptor-activated Gβγ and polarity regulators. Artificially blocking patch wandering impairs gradient tracking. CONCLUSIONS We suggest that the polarity patch undergoes an intracellular biased random walk that enables noise filtering by time averaging, allowing nonmotile cells to track shallow gradients.

[1]  David E. Stone,et al.  Polarization of the Yeast Pheromone Receptor Requires Its Internalization but Not Actin-dependent Secretion , 2010, Molecular biology of the cell.

[2]  Navin Pokala,et al.  High Rates of Actin Filament Turnover in Budding Yeast and Roles for Actin in Establishment and Maintenance of Cell Polarity Revealed Using the Actin Inhibitor Latrunculin-A , 1997, The Journal of cell biology.

[3]  Anita T. Layton,et al.  Modeling Vesicle Traffic Reveals Unexpected Consequences for Cdc42p-Mediated Polarity Establishment , 2011, Current Biology.

[4]  P. Pryciak,et al.  Distinct roles for two Galpha-Gbeta interfaces in cell polarity control by a yeast heterotrimeric G protein. , 2008, Molecular biology of the cell.

[5]  I. Herskowitz,et al.  The role of Far1p in linking the heterotrimeric G protein to polarity establishment proteins during yeast mating. , 1998, Science.

[6]  Brian D. Slaughter,et al.  Dual modes of cdc42 recycling fine-tune polarized morphogenesis. , 2009, Developmental cell.

[7]  Eugenio Marco,et al.  Endocytosis Optimizes the Dynamic Localization of Membrane Proteins that Regulate Cortical Polarity , 2007, Cell.

[8]  V. Nanjundiah,et al.  Signal input for a chemotactic response in the cellular slime mold Dictyostelium discoideum. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[9]  M. Snyder,et al.  Spa2p Interacts with Cell Polarity Proteins and Signaling Components Involved in Yeast Cell Morphogenesis , 1998, Molecular and Cellular Biology.

[10]  Qing Nie,et al.  Noise filtering tradeoffs in spatial gradient sensing and cell polarization response , 2011, BMC Systems Biology.

[11]  David G. Drubin,et al.  A role for the yeast actin cytoskeleton in pheromone receptor clustering and signalling , 1998, Current Biology.

[12]  Matthias Peter,et al.  The nucleotide exchange factor Cdc24p may be regulated by auto‐inhibition , 2004, The EMBO journal.

[13]  Aljoscha Nern,et al.  A Cdc24p-Far1p-Gβγ Protein Complex Required for Yeast Orientation during Mating , 1999, The Journal of cell biology.

[14]  P. V. van Haastert,et al.  Biased random walk by stochastic fluctuations of chemoattractant-receptor interactions at the lower limit of detection. , 2007, Biophysical journal.

[15]  Michael Snyder,et al.  Specification of sites for polarized growth in Saccharomyces cerevisiae and the influence of external factors on site selection. , 1992, Molecular biology of the cell.

[16]  J. Hasty,et al.  Regulation of cell signaling dynamics by the protein kinase-scaffold Ste5. , 2008, Molecular cell.

[17]  J. Segall,et al.  Polarization of yeast cells in spatial gradients of alpha mating factor. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[18]  I. Herskowitz,et al.  FAR1 is required for oriented polarization of yeast cells in response to mating pheromones , 1995, The Journal of cell biology.

[19]  Zigmond Sh.  Ability of polymorphonuclear leukocytes to orient in gradients of chemotactic factors. , 1977 .

[20]  A. Nern,et al.  G proteins mediate changes in cell shape by stabilizing the axis of polarity. , 2000, Molecular cell.

[21]  E. Bi,et al.  Cell Polarization and Cytokinesis in Budding Yeast , 2012, Genetics.

[22]  I. Shmulevich,et al.  High-throughput tracking of single yeast cells in a microfluidic imaging matrix. , 2011, Lab on a chip.

[23]  P. Pryciak,et al.  Distinct Roles for Two Gα–Gβ Interfaces in Cell Polarity Control by a Yeast Heterotrimeric G Protein , 2008 .

[24]  A. Bretscher,et al.  Mechanisms of polarized growth and organelle segregation in yeast. , 2004, Annual review of cell and developmental biology.

[25]  I. Herskowitz,et al.  Two active states of the Ras-related Bud1/Rsr1 protein bind to different effectors to determine yeast cell polarity. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Chuan-Hsiang Huang,et al.  Eukaryotic chemotaxis: a network of signaling pathways controls motility, directional sensing, and polarity. , 2010, Annual review of biophysics.

[27]  Matthias Peter,et al.  Phosphorylation of Bem2p and Bem3p may contribute to local activation of Cdc42p at bud emergence , 2007, The EMBO journal.

[28]  R. Arkowitz,et al.  Chemical gradients and chemotropism in yeast. , 2009, Cold Spring Harbor perspectives in biology.

[29]  Toshio Yanagida,et al.  Stochastic signal inputs for chemotactic response in Dictyostelium cells revealed by single molecule imaging techniques , 2007, Biosyst..

[30]  S. Zigmond,et al.  ABILITY OF POLYMORPHONUCLEAR LEUKOCYTES TO ORIENT IN GRADIENTS OF CHEMOTACTIC FACTORS , 2003 .

[31]  Andrew B Goryachev,et al.  Dynamics of Cdc42 network embodies a Turing‐type mechanism of yeast cell polarity , 2008, FEBS letters.

[32]  M. Peter,et al.  Site‐specific regulation of the GEF Cdc24p by the scaffold protein Far1p during yeast mating , 2004, The EMBO journal.

[33]  Roland Wedlich-Söldner,et al.  Cortical actin dynamics driven by formins and myosin V , 2011, Journal of Cell Science.

[34]  Comparison of dose-response curves for alpha factor-induced cell division arrest, agglutination, and projection formation of yeast cells. Implication for the mechanism of alpha factor action. , 1983, The Journal of biological chemistry.

[35]  Alexander van Oudenaarden,et al.  A system of counteracting feedback loops regulates Cdc42p activity during spontaneous cell polarization. , 2005, Developmental cell.

[36]  L. Marsh,et al.  A Role for a Protease in Morphogenic Responses during Yeast Cell Fusion , 1998, The Journal of cell biology.

[37]  Jayme M. Johnson,et al.  Symmetry breaking and the establishment of cell polarity in budding yeast. , 2011, Current opinion in genetics & development.

[38]  Qing Nie,et al.  Robust Spatial Sensing of Mating Pheromone Gradients by Yeast Cells , 2008, PloS one.

[39]  G. Wadhams,et al.  Making sense of it all: bacterial chemotaxis , 2004, Nature Reviews Molecular Cell Biology.

[40]  Indrani Bose,et al.  Singularity in Polarization: Rewiring Yeast Cells to Make Two Buds , 2009, Cell.

[41]  Anita T. Layton,et al.  Mechanistic mathematical model of polarity in yeast , 2012, Molecular biology of the cell.

[42]  Timothy C. Elston,et al.  Negative Feedback Enhances Robustness in the Yeast Polarity Establishment Circuit , 2012, Cell.

[43]  Sophie G. Martin,et al.  Cdc42 Explores the Cell Periphery for Mate Selection in Fission Yeast , 2013, Current Biology.

[44]  A. Bretscher,et al.  The Cooh-Terminal Domain of Myo2p, a Yeast Myosin V, Has a Direct Role in Secretory Vesicle Targeting , 1999, The Journal of cell biology.