Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Science 299 (5610): 1231-1235

Copyright © 2003 by the American Association for the Advancement of Science

Spontaneous Cell Polarization Through Actomyosin-Based Delivery of the Cdc42 GTPase

Roland Wedlich-Soldner,1 Steve Altschuler,2 Lani Wu,2 Rong Li1*

Cell polarization can occur in the absence of any spatial cues. To investigate the mechanism of spontaneous cell polarization, we used an assay in yeast where expression of an activated form of Cdc42, a Rho-type guanosine triphosphatase (GTPase) required for cell polarization, could generate cell polarity without any recourse to a preestablished physical cue. The polar distribution of Cdc42 in this assay required targeted secretion directed by the actin cytoskeleton. A mathematical simulation showed that a stable polarity axis could be generated through a positive feedback loop in which a stochastic increase in the local concentration of activated Cdc42 on the plasma membrane enhanced the probability of actin polymerization and increased the probability of further Cdc42 accumulation to that site.

1 Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
2 Bauer Center for Genomics Research, Harvard University, Cambridge, MA 02138, USA.
*   To whom correspondence should be addressed. E-mail: rong_li{at}hms.harvard.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Robust polarity establishment occurs via an endocytosis-based cortical corralling mechanism.
M. Jose, S. Tollis, D. Nair, J.-B. Sibarita, and D. McCusker (2013)
J. Cell Biol. 200, 407-418
   Abstract »    Full Text »    PDF »
Quantitative Analysis of Prenylated RhoA Interaction with Its Chaperone, RhoGDI.
Z. Tnimov, Z. Guo, Y. Gambin, U. T. T. Nguyen, Y.-W. Wu, D. Abankwa, A. Stigter, B. M. Collins, H. Waldmann, R. S. Goody, et al. (2012)
J. Biol. Chem. 287, 26549-26562
   Abstract »    Full Text »    PDF »
Cell Polarization and Cytokinesis in Budding Yeast.
E. Bi and H.-O. Park (2012)
Genetics 191, 347-387
   Abstract »    Full Text »    PDF »
Mechanistic mathematical model of polarity in yeast.
N. S. Savage, A. T. Layton, and D. J. Lew (2012)
Mol. Biol. Cell 23, 1998-2013
   Abstract »    Full Text »    PDF »
Cell Polarity: Quantitative Modeling as a Tool in Cell Biology.
A. Mogilner, J. Allard, and R. Wollman (2012)
Science 336, 175-179
   Abstract »    Full Text »    PDF »
Morphogenesis and the Cell Cycle.
A. S. Howell and D. J. Lew (2012)
Genetics 190, 51-77
   Abstract »    Full Text »    PDF »
Rong Li: Tipping the balance in cell biology.
C. Sedwick (2011)
J. Cell Biol. 195, 1068-1069
   Full Text »    PDF »
Cla4 kinase triggers destruction of the Rac1-GEF Cdc24 during polarized growth in Ustilago maydis.
S. H. Frieser, A. Hlubek, B. Sandrock, and M. Bolker (2011)
Mol. Biol. Cell 22, 3253-3262
   Abstract »    Full Text »    PDF »
PAR proteins diffuse freely across the anterior-posterior boundary in polarized C. elegans embryos.
N. W. Goehring, C. Hoege, S. W. Grill, and A. A. Hyman (2011)
J. Cell Biol. 193, 583-594
   Abstract »    Full Text »    PDF »
Cortical actin dynamics driven by formins and myosin V.
J. H. Yu, A. H. Crevenna, M. Bettenbuhl, T. Freisinger, and R. Wedlich-Soldner (2011)
J. Cell Sci. 124, 1533-1541
   Abstract »    Full Text »    PDF »
Exo-endocytic trafficking and the septin-based diffusion barrier are required for the maintenance of Cdc42p polarization during budding yeast asymmetric growth.
K. Orlando, X. Sun, J. Zhang, T. Lu, L. Yokomizo, P. Wang, and W. Guo (2011)
Mol. Biol. Cell 22, 624-633
   Abstract »    Full Text »    PDF »
Cdc42 localization and cell polarity depend on membrane traffic.
N. Osmani, F. Peglion, P. Chavrier, and S. Etienne-Manneville (2010)
J. Cell Biol. 191, 1261-1269
   Abstract »    Full Text »    PDF »
The Function of Two Rho Family GTPases Is Determined by Distinct Patterns of Cell Surface Localization.
H. Wu and P. Brennwald (2010)
Mol. Cell. Biol. 30, 5207-5217
   Abstract »    Full Text »    PDF »
Endocytic Machinery Protein SlaB Is Dispensable for Polarity Establishment but Necessary for Polarity Maintenance in Hyphal Tip Cells of Aspergillus nidulans.
A. Hervas-Aguilar and M. A. Penalva (2010)
Eukaryot. Cell 9, 1504-1518
   Abstract »    Full Text »    PDF »
Secretion is required for late events in the cell-fusion pathway of mating yeast.
E. Grote (2010)
J. Cell Sci. 123, 1902-1912
   Abstract »    Full Text »    PDF »
Rab35 Mediates Transport of Cdc42 and Rac1 to the Plasma Membrane during Phagocytosis.
J. Shim, S.-M. Lee, M. S. Lee, J. Yoon, H.-S. Kweon, and Y.-J. Kim (2010)
Mol. Cell. Biol. 30, 1421-1433
   Abstract »    Full Text »    PDF »
Pollen-tube tip growth requires a balance of lateral propagation and global inhibition of Rho-family GTPase activity.
J.-U. Hwang, G. Wu, A. Yan, Y.-J. Lee, C. S. Grierson, and Z. Yang (2010)
J. Cell Sci. 123, 340-350
   Abstract »    Full Text »    PDF »
Membrane Organization and Dynamics in Cell Polarity.
K. Orlando and W. Guo (2009)
Cold Spring Harb Perspect Biol 1, a001321
   Abstract »    Full Text »    PDF »
Neuronal Polarity.
S. Tahirovic and F. Bradke (2009)
Cold Spring Harb Perspect Biol 1, a001644
   Abstract »    Full Text »    PDF »
Symmetry Breaking in the Life Cycle of the Budding Yeast.
B. D. Slaughter, S. E. Smith, and R. Li (2009)
Cold Spring Harb Perspect Biol 1, a003384
   Abstract »    Full Text »    PDF »
New Insights into How the Rho Guanine Nucleotide Dissociation Inhibitor Regulates the Interaction of Cdc42 with Membranes.
J. L. Johnson, J. W. Erickson, and R. A. Cerione (2009)
J. Biol. Chem. 284, 23860-23871
   Abstract »    Full Text »    PDF »
Chemical Gradients and Chemotropism in Yeast.
R. A. Arkowitz (2009)
Cold Spring Harb Perspect Biol 1, a001958
   Abstract »    Full Text »    PDF »
The Class V Myosin Myo2p Is Required for Fus2p Transport and Actin Polarization during the Yeast Mating Response.
J. M. Sheltzer and M. D. Rose (2009)
Mol. Biol. Cell 20, 2909-2919
   Abstract »    Full Text »    PDF »
Growth-speed-correlated localization of exocyst and polarisome components in growth zones of Ashbya gossypii hyphal tips.
M. Kohli, V. Galati, K. Boudier, R. W. Roberson, and P. Philippsen (2008)
J. Cell Sci. 121, 3878-3889
   Abstract »    Full Text »    PDF »
Branching of fungal hyphae: regulation, mechanisms and comparison with other branching systems.
S. D. Harris (2008)
Mycologia 100, 823-832
   Abstract »    Full Text »    PDF »
RIP1 (ROP Interactive Partner 1)/ICR1 Marks Pollen Germination Sites and May Act in the ROP1 Pathway in the Control of Polarized Pollen Growth.
S. Li, Y. Gu, A. Yan, E. Lord, and Z.-B. Yang (2008)
Mol Plant 1, 1021-1035
   Abstract »    Full Text »    PDF »
Swf1p, a Member of the DHHC-CRD Family of Palmitoyltransferases, Regulates the Actin Cytoskeleton and Polarized Secretion Independently of Its DHHC Motif.
S. A. Dighe and K. G. Kozminski (2008)
Mol. Biol. Cell 19, 4454-4468
   Abstract »    Full Text »    PDF »
Aspergillus nidulans ArfB Plays a Role in Endocytosis and Polarized Growth.
S. C. Lee, S. N. Schmidtke, L. J. Dangott, and B. D. Shaw (2008)
Eukaryot. Cell 7, 1278-1288
   Abstract »    Full Text »    PDF »
Cell polarization during monopolar cytokinesis.
C.-K. Hu, M. Coughlin, C. M. Field, and T. J. Mitchison (2008)
J. Cell Biol. 181, 195-202
   Abstract »    Full Text »    PDF »
Distinct Roles for Two G{alpha}-G{beta} Interfaces in Cell Polarity Control by a Yeast Heterotrimeric G Protein.
S. C. Strickfaden and P. M. Pryciak (2008)
Mol. Biol. Cell 19, 181-197
   Abstract »    Full Text »    PDF »
Microtubules offset growth site from the cell centre in fission yeast.
S. Castagnetti, B. Novak, and P. Nurse (2007)
J. Cell Sci. 120, 2205-2213
   Abstract »    Full Text »    PDF »
Candida albicans hyphal morphogenesis occurs in Sec3p-independent and Sec3p-dependent phases separated by septin ring formation.
C.-R. Li, R. T.-H. Lee, Y.-M. Wang, X.-D. Zheng, and Y. Wang (2007)
J. Cell Sci. 120, 1898-1907
   Abstract »    Full Text »    PDF »
mRNAs Encoding Polarity and Exocytosis Factors Are Cotransported with the Cortical Endoplasmic Reticulum to the Incipient Bud in Saccharomyces cerevisiae.
S. Aronov, R. Gelin-Licht, G. Zipor, L. Haim, E. Safran, and J. E. Gerst (2007)
Mol. Cell. Biol. 27, 3441-3455
   Abstract »    Full Text »    PDF »
Sustained cell polarity and virulence in the phytopathogenic fungus Ustilago maydis depends on an essential cyclin-dependent kinase from the Cdk5/Pho85 family.
S. Castillo-Lluva, I. Alvarez-Tabares, I. Weber, G. Steinberg, and J. Perez-Martin (2007)
J. Cell Sci. 120, 1584-1595
   Abstract »    Full Text »    PDF »
Avl9p, a Member of a Novel Protein Superfamily, Functions in the Late Secretory Pathway.
E. Harsay and R. Schekman (2007)
Mol. Biol. Cell 18, 1203-1219
   Abstract »    Full Text »    PDF »
Asymmetric Distribution of Prickle-Like 2 Reveals an Early Underlying Polarization of Vestibular Sensory Epithelia in the Inner Ear.
M. R. Deans, D. Antic, K. Suyama, M. P. Scott, J. D. Axelrod, and L. V. Goodrich (2007)
J. Neurosci. 27, 3139-3147
   Abstract »    Full Text »    PDF »
Central Roles of Small GTPases in the Development of Cell Polarity in Yeast and Beyond.
H.-O. Park and E. Bi (2007)
Microbiol. Mol. Biol. Rev. 71, 48-96
   Abstract »    Full Text »    PDF »
Cracking up: symmetry breaking in cellular systems.
E. Paluch, J. van der Gucht, and C. Sykes (2006)
J. Cell Biol. 175, 687-692
   Abstract »    Full Text »    PDF »
Epsin N-terminal homology domains perform an essential function regulating Cdc42 through binding Cdc42 GTPase-activating proteins.
R. C. Aguilar, S. A. Longhi, J. D. Shaw, L.-Y. Yeh, S. Kim, A. Schon, E. Freire, A. Hsu, W. K. McCormick, H. A. Watson, et al. (2006)
PNAS 103, 4116-4121
   Abstract »    Full Text »    PDF »
Role of a Cdc42p Effector Pathway in Recruitment of the Yeast Septins to the Presumptive Bud Site.
M. Iwase, J. Luo, S. Nagaraj, M. Longtine, H. B. Kim, B. K. Haarer, C. Caruso, Z. Tong, J. R. Pringle, and E. Bi (2006)
Mol. Biol. Cell 17, 1110-1125
   Abstract »    Full Text »    PDF »
Oscillatory ROP GTPase Activation Leads the Oscillatory Polarized Growth of Pollen Tubes.
J.-U. Hwang, Y. Gu, Y.-J. Lee, and Z. Yang (2005)
Mol. Biol. Cell 16, 5385-5399
   Abstract »    Full Text »    PDF »
Interlinked Fast and Slow Positive Feedback Loops Drive Reliable Cell Decisions.
O. Brandman, J. E. Ferrell Jr., R. Li, and T. Meyer (2005)
Science 310, 496-498
   Abstract »    Full Text »    PDF »
Regulation of Cell Polarity by Interactions of Msb3 and Msb4 with Cdc42 and Polarisome Components.
S. E. Tcheperegine, X.-D. Gao, and E. Bi (2005)
Mol. Cell. Biol. 25, 8567-8580
   Abstract »    Full Text »    PDF »
Rho GTPase regulation of exocytosis in yeast is independent of GTP hydrolysis and polarization of the exocyst complex.
O. Roumanie, H. Wu, J. N. Molk, G. Rossi, K. Bloom, and P. Brennwald (2005)
J. Cell Biol. 170, 583-594
   Abstract »    Full Text »    PDF »
Role of the Septin Ring in the Asymmetric Localization of Proteins at the Mother-Bud Neck in Saccharomyces cerevisiae.
L. Kozubowski, J. R. Larson, and K. Tatchell (2005)
Mol. Biol. Cell 16, 3455-3466
   Abstract »    Full Text »    PDF »
The Pleckstrin Homology Domain Proteins Slm1 and Slm2 Are Required for Actin Cytoskeleton Organization in Yeast and Bind Phosphatidylinositol-4,5-Bisphosphate and TORC2.
M. Fadri, A. Daquinag, S. Wang, T. Xue, and J. Kunz (2005)
Mol. Biol. Cell 16, 1883-1900
   Abstract »    Full Text »    PDF »
Ste20/GCK kinase Nak1/Orb3 polarizes the actin cytoskeleton in fission yeast during the cell cycle.
K. Leonhard and P. Nurse (2005)
J. Cell Sci. 118, 1033-1044
   Abstract »    Full Text »    PDF »
Opposing Roles for Actin in Cdc42p Polarization.
J. E. Irazoqui, A. S. Howell, C. L. Theesfeld, and D. J. Lew (2005)
Mol. Biol. Cell 16, 1296-1304
   Abstract »    Full Text »    PDF »
Cyclical Regulation of the Exocyst and Cell Polarity Determinants for Polarized Cell Growth.
A. Zajac, X. Sun, J. Zhang, and W. Guo (2005)
Mol. Biol. Cell 16, 1500-1512
   Abstract »    Full Text »    PDF »
Stable and Dynamic Axes of Polarity Use Distinct Formin Isoforms in Budding Yeast.
D. Pruyne, L. Gao, E. Bi, and A. Bretscher (2004)
Mol. Biol. Cell 15, 4971-4989
   Abstract »    Full Text »    PDF »
A Ras-like GTPase Is Involved in Hyphal Growth Guidance in the Filamentous Fungus Ashbya gossypii.
Y. Bauer, P. Knechtle, J. Wendland, H. Helfer, and P. Philippsen (2004)
Mol. Biol. Cell 15, 4622-4632
   Abstract »    Full Text »    PDF »
Robust cell polarity is a dynamic state established by coupling transport and GTPase signaling.
R. Wedlich-Soldner, S. C. Wai, T. Schmidt, and R. Li (2004)
J. Cell Biol. 166, 889-900
   Abstract »    Full Text »    PDF »
Activation of Endogenous Cdc42 Visualized in Living Cells.
P. Nalbant, L. Hodgson, V. Kraynov, A. Toutchkine, and K. M. Hahn (2004)
Science 305, 1615-1619
   Abstract »    Full Text »    PDF »
Involvement of the Late Secretory Pathway in Actin Regulation and mRNA Transport in Yeast.
S. Aronov and J. E. Gerst (2004)
J. Biol. Chem. 279, 36962-36971
   Abstract »    Full Text »    PDF »
MesA, a Novel Fungal Protein Required for the Stabilization of Polarity Axes in Aspergillus nidulans.
C. L. Pearson, K. Xu, K. E. Sharpless, and S. D. Harris (2004)
Mol. Biol. Cell 15, 3658-3672
   Abstract »    Full Text »    PDF »
A signaling mucin at the head of the Cdc42- and MAPK-dependent filamentous growth pathway in yeast.
P. J. Cullen, W. Sabbagh Jr., E. Graham, M. M. Irick, E. K. van Olden, C. Neal, J. Delrow, L. Bardwell, and G. F. Sprague Jr. (2004)
Genes & Dev. 18, 1695-1708
   Abstract »    Full Text »    PDF »
Cdc50p, a Protein Required for Polarized Growth, Associates with the Drs2p P-Type ATPase Implicated in Phospholipid Translocation in Saccharomyces cerevisiae.
K. Saito, K. Fujimura-Kamada, N. Furuta, U. Kato, M. Umeda, and K. Tanaka (2004)
Mol. Biol. Cell 15, 3418-3432
   Abstract »    Full Text »    PDF »
EBV attachment stimulates FHOS/FHOD1 redistribution and co-aggregation with CD21: formin interactions with the cytoplasmic domain of human CD21.
M. B. Gill, J. Roecklein-Canfield, D. R. Sage, M. Zambela-Soediono, N. Longtine, M. Uknis, and J. D. Fingeroth (2004)
J. Cell Sci. 117, 2709-2720
   Abstract »    Full Text »    PDF »
Cdc42 - the centre of polarity.
S. Etienne-Manneville (2004)
J. Cell Sci. 117, 1291-1300
   Abstract »    Full Text »    PDF »
Regulation of polarized growth initiation and termination cycles by the polarisome and Cdc42 regulators.
S. Bidlingmaier and M. Snyder (2004)
J. Cell Biol. 164, 207-218
   Abstract »    Full Text »    PDF »
The GAP activity of Msb3p and Msb4p for the Rab GTPase Sec4p is required for efficient exocytosis and actin organization.
X.-D. Gao, S. Albert, S. E. Tcheperegine, C. G. Burd, D. Gallwitz, and E. Bi (2003)
J. Cell Biol. 162, 635-646
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882