GDI-Mediated Cell Polarization in Yeast Provides Precise Spatial and Temporal Control of Cdc42 Signaling
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{"title"=>"GDI-Mediated Cell Polarization in Yeast Provides Precise Spatial and Temporal Control of Cdc42 Signaling", "type"=>"journal", "authors"=>[{"first_name"=>"Ben", "last_name"=>"Klünder", "scopus_author_id"=>"26428250700"}, {"first_name"=>"Tina", "last_name"=>"Freisinger", "scopus_author_id"=>"24775738300"}, {"first_name"=>"Roland", "last_name"=>"Wedlich-Söldner", "scopus_author_id"=>"6506102218"}, {"first_name"=>"Erwin", "last_name"=>"Frey", "scopus_author_id"=>"7103012792"}], "year"=>2013, "source"=>"PLoS Computational Biology", "identifiers"=>{"sgr"=>"84892727960", "doi"=>"10.1371/journal.pcbi.1003396", "pui"=>"372170459", "pmid"=>"24348237", "scopus"=>"2-s2.0-84892727960", "issn"=>"1553734X", "isbn"=>"1553-7358 (Electronic) 1553-734X (Linking)"}, "id"=>"d2f442a3-23f2-371a-bba5-e27d8ab94af9", "abstract"=>"Cell polarization is a prerequisite for essential processes such as cell migration, proliferation or differentiation. The yeast Saccharomyces cerevisiae under control of the GTPase Cdc42 is able to polarize without the help of cytoskeletal structures and spatial cues through a pathway depending on its guanine nucleotide dissociation inhibitor (GDI) Rdi1. To develop a fundamental understanding of yeast polarization we establish a detailed mechanistic model of GDI-mediated polarization. We show that GDI-mediated polarization provides precise spatial and temporal control of Cdc42 signaling and give experimental evidence for our findings. Cell cycle induced changes of Cdc42 regulation enhance positive feedback loops of active Cdc42 production, and thereby allow simultaneous switch-like regulation of focused polarity and Cdc42 activation. This regulation drives the direct formation of a unique polarity cluster with characteristic narrowing dynamics, as opposed to the previously proposed competition between transient clusters. As the key components of the studied system are conserved among eukaryotes, we expect our findings also to apply to cell polarization in other organisms.", "link"=>"http://www.mendeley.com/research/gdimediated-cell-polarization-yeast-provides-precise-spatial-temporal-control-cdc42-signaling", "reader_count"=>57, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>4, "Researcher"=>13, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>4, "Student > Master"=>6, "Other"=>1, "Student > Bachelor"=>5, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>4, "Researcher"=>13, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>4, "Student > Master"=>6, "Other"=>1, "Student > Bachelor"=>5, "Professor"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>12, "Agricultural and Biological Sciences"=>19, "Medicine and Dentistry"=>1, "Physics and Astronomy"=>19, "Chemical Engineering"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>19}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>19}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>12}, "Unspecified"=>{"Unspecified"=>2}, "Chemical Engineering"=>{"Chemical Engineering"=>1}}, "reader_count_by_country"=>{"Netherlands"=>2, "United States"=>1, "Germany"=>1}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1313844", "https://ndownloader.figshare.com/files/1313846", "https://ndownloader.figshare.com/files/1313847", "https://ndownloader.figshare.com/files/1313848", "https://ndownloader.figshare.com/files/1313849", "https://ndownloader.figshare.com/files/1313850", "https://ndownloader.figshare.com/files/1313851", "https://ndownloader.figshare.com/files/1313852"], "description"=>"<div><p>Cell polarization is a prerequisite for essential processes such as cell migration, proliferation or differentiation. The yeast <i>Saccharomyces cerevisiae</i> under control of the GTPase Cdc42 is able to polarize without the help of cytoskeletal structures and spatial cues through a pathway depending on its guanine nucleotide dissociation inhibitor (GDI) Rdi1. To develop a fundamental understanding of yeast polarization we establish a detailed mechanistic model of GDI-mediated polarization. We show that GDI-mediated polarization provides precise spatial and temporal control of Cdc42 signaling and give experimental evidence for our findings. Cell cycle induced changes of Cdc42 regulation enhance positive feedback loops of active Cdc42 production, and thereby allow simultaneous switch-like regulation of focused polarity and Cdc42 activation. This regulation drives the direct formation of a unique polarity cluster with characteristic narrowing dynamics, as opposed to the previously proposed competition between transient clusters. As the key components of the studied system are conserved among eukaryotes, we expect our findings also to apply to cell polarization in other organisms.</p></div>", "links"=>[], "tags"=>["polarization", "yeast", "provides", "spatial", "temporal", "cdc42"], "article_id"=>876798, "categories"=>["Biological Sciences"], "users"=>["Ben Klünder", "Tina Freisinger", "Roland Wedlich-Söldner", "Erwin Frey"], "doi"=>["https://dx.doi.org/10.1371/journal.pcbi.1003396.s001", "https://dx.doi.org/10.1371/journal.pcbi.1003396.s002", "https://dx.doi.org/10.1371/journal.pcbi.1003396.s003", "https://dx.doi.org/10.1371/journal.pcbi.1003396.s004", "https://dx.doi.org/10.1371/journal.pcbi.1003396.s005", "https://dx.doi.org/10.1371/journal.pcbi.1003396.s006", "https://dx.doi.org/10.1371/journal.pcbi.1003396.s007", "https://dx.doi.org/10.1371/journal.pcbi.1003396.s008"], "stats"=>{"downloads"=>4, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GDI_Mediated_Cell_Polarization_in_Yeast_Provides_Precise_Spatial_and_Temporal_Control_of_Cdc42_Signaling_/876798", "title"=>"GDI-Mediated Cell Polarization in Yeast Provides Precise Spatial and Temporal Control of Cdc42 Signaling", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-12-12 04:42:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/1313829"], "description"=>"<p><b>A</b> Schematic representation of model reactions. A list of all model reactions is given in the <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003396#s4\" target=\"_blank\">Materials and Methods</a> section. <b>B</b> Numerically obtained polarized Cdc42 distribution on the membrane for control conditions. <b>C</b> Corresponding cytosolic distribution of Cdc42 in the x-z plane. Arrows indicate protein flux.</p>", "links"=>[], "tags"=>["mechanistic", "gdi-mediated", "polarization"], "article_id"=>876783, "categories"=>["Biological Sciences"], "users"=>["Ben Klünder", "Tina Freisinger", "Roland Wedlich-Söldner", "Erwin Frey"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003396.g001", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Details_of_the_mechanistic_model_for_GDI_mediated_cell_polarization_in_yeast_/876783", "title"=>"Details of the mechanistic model for GDI-mediated cell polarization in yeast.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-12 04:42:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/1313830"], "description"=>"<p><b>A</b> Cdc42 density on the plasma membrane for different points in time as obtained from numerical simulations (<a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003396#pcbi.1003396.s002\" target=\"_blank\">Movie S1</a>) starting from the unpolarized homogenous solution disturbed by a small random perturbation using control cell parameters. <b>B</b> Development of simulated Cdc42 cluster height (maximum density over background) over time starting with a random initial perturbation (green curve) or using a broad cap as initial perturbation (blue curve). The black lines correspond to a growth rate of the corresponding cluster of 0.00417 s<sup>−1</sup> as predicted from the linear stability analysis. <b>C</b> Full width at half maximum (FWHM) of simulated Cdc42 cluster height measured along a great circle through the cap center over circumference 2πR (blue) and simulated Cdc42 cluster height (green) with a broad faint cap as initial perturbation for different points in time.</p>", "links"=>[], "tags"=>["gdi-mediated"], "article_id"=>876784, "categories"=>["Biological Sciences"], "users"=>["Ben Klünder", "Tina Freisinger", "Roland Wedlich-Söldner", "Erwin Frey"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003396.g002", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Predicted_dynamics_of_GDI_mediated_polarization_/876784", "title"=>"Predicted dynamics of GDI-mediated polarization.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-12 04:42:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/1313839"], "description"=>"<p><b>A–D</b> Full width at half maximum of Cdc42 density as obtained in <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003396#pcbi-1003396-g002\" target=\"_blank\">Figure 2</a> for different Cdc24 (A) and Bem1 (B) concentrations, as well as for different Cdc42 extraction (C) and hydrolysis (D) rates. Arrows indicate the corresponding control cell values. <b>E</b> Examples of Cdc42 cluster density calculated for different hydrolysis rates. <b>F, G</b> Images and quantification of GFP-Cdc42 cap widths in control and Δ<i>bem2</i> cells in the presence (F, unpaired t-test with Welch correction, p<0.001) or absence (G, unpaired t-test with Welch correction, p = 0.01) of latrunculin B. Broad caps are also seen in cells expressing a slowly hydrolyzing GFP-Cdc42<sup>G60A</sup> mutant. Images and cap widths were acquired 30–50 min after release from G1 arrest. Bar graphs correspond to mean ± SEM. Scale bars: 4 µm.</p>", "links"=>[], "tags"=>["widths"], "article_id"=>876793, "categories"=>["Biological Sciences"], "users"=>["Ben Klünder", "Tina Freisinger", "Roland Wedlich-Söldner", "Erwin Frey"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003396.g005", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cluster_widths_for_changing_parameters_and_experimental_verification_/876793", "title"=>"Cluster widths for changing parameters and experimental verification.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-12 04:42:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/1313833"], "description"=>"<p><b>A,B</b> Polarization capability predicted from the linear stability analysis shown for different concentrations of the GEF Cdc24 and Cdc42 hydrolysis rates (A) as well as for different concentrations of Bem1 protein and Cdc42 extraction rates (B). In addition, parameter regions are shown where polarization cannot be rescued by a change of the diffusion constants D<sub>2</sub>, D<sub>3</sub>. Black dots indicate values in control cells. <b>C,D</b> Plots as in (A, B) but in addition indicating concentration of membrane-bound Cdc42-GTP (as fraction of total cellular Cdc42) in unpolarized cells. Black dots indicate values in control cells. <b>E,F</b> Concentration of membrane-bound Cdc42-GTP for different Cdc42 hydrolysis rates (E) and Cdc24 protein numbers per cell (F). The arrows indicate the control cell values. <b>G</b> Comparison of average intensity and polarization efficiency of latrunculin B-treated control and Δ<i>bem1</i> cells expressing Bem1-GFP from the endogenous or the weak Cdc24 or Abp140 promoter. ANOVA, F(2,6) = 25.52: P = 0.0012, Dunnett's posthoc: control-p24: p<0.001, control-pAbp140: p<0.01. <b>H</b> Polarization efficiency of GFP-Cdc42 control cells treated with latrunculin B without or with the overexpression of Rdi1. Rdi1 was either overexpressed as an additional copy under its endogenous promoter or under the Gal-promoter. Unpaired t-test with Welch correction: control - pRDI1-Rdi1RFP: p<0.001, control - pGal-Rdi1: p = 0.015.</p>", "links"=>[], "tags"=>["affecting", "polarization", "cdc42"], "article_id"=>876787, "categories"=>["Biological Sciences"], "users"=>["Ben Klünder", "Tina Freisinger", "Roland Wedlich-Söldner", "Erwin Frey"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003396.g004", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Parameters_affecting_polarization_efficiency_and_Cdc42_activation_/876787", "title"=>"Parameters affecting polarization efficiency and Cdc42 activation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-12 04:42:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/1313832"], "description"=>"<p><b>A,B</b> Representative images and cap intensity profiles of latrunculin B-treated control cells expressing GFP-Cdc42 at an early (20–30 min after release, A) and late (30–50 min after release, B) time point during polarization. <b>C</b> Comparison of full width at half maximum (FWHM) of GFP-Cdc42 + latrunculin B caps at early (N = 13, SEM = 0.15; 20–30 min after release) and late time points (N = 28, SEM = 0.10; 30–50 min after release), unpaired t-test with Welch correction, p<0.001. <b>D</b> Time series showing GFP-Cdc42 cap establishment in a control cell treated with latrunculin B (<a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003396#pcbi.1003396.s003\" target=\"_blank\">Movie S2</a>, every second frame starting from frame 12, 30 s time steps between frames). <b>E</b> Time evolution of full width at half maximum of GFP-Cdc42 cap shown in (D) and <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003396#pcbi.1003396.s003\" target=\"_blank\">Movie S2</a> (first width corresponds to frame 10 of <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003396#pcbi.1003396.s003\" target=\"_blank\">Movie S2</a>). <b>F</b> Time series showing Bem1-GFP cap establishment in a control cell treated with latrunculin B (<a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003396#pcbi.1003396.s004\" target=\"_blank\">Movie S3</a>, every frame starting from frame 8, 60 s time steps between frames). <b>G</b> Time evolution of full width at half maximum of Bem1-GFP cap shown in (F) and <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003396#pcbi.1003396.s004\" target=\"_blank\">Movie S3</a> (first width corresponds to frame 8 of <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003396#pcbi.1003396.s004\" target=\"_blank\">Movie S3</a>). Scale bars: 4 µm.</p>", "links"=>[], "tags"=>["characterization", "gdi-mediated"], "article_id"=>876786, "categories"=>["Biological Sciences"], "users"=>["Ben Klünder", "Tina Freisinger", "Roland Wedlich-Söldner", "Erwin Frey"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003396.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Experimental_characterization_of_GDI_mediated_polarization_/876786", "title"=>"Experimental characterization of GDI-mediated polarization.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-12 04:42:12"}

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  • {"unique-ip"=>"13", "full-text"=>"20", "pdf"=>"15", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"14", "full-text"=>"11", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"13", "full-text"=>"18", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"12", "full-text"=>"9", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}

Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Physical sciences/Chemistry", "average_usage"=>[247, 429, 544, 647, 747, 842, 929, 1012, 1099, 1179, 1263, 1339, 1409]}]}
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