|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
COMMENTARY |
The Scripps Research Institute, Department of Cell Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
*Author for correspondence (e-mail: waterman{at}scripps.edu)
Migrating cells display a characteristic polarization of the actin cytoskeleton. Actin filaments polymerise in the protruding front of the cell whereas actin filament bundles contract in the cell body, which results in retraction of the cells rear. The dynamic organization of the actin cytoskeleton provides the force for cell motility and is regulated by small GTPases of the Rho family, in particular Rac1, RhoA and Cdc42. Although the microtubule cytoskeleton is also polarized in a migrating cell, and microtubules are essential for the directed migration of many cell types, their role in cell motility is not well understood at a molecular level. Here, we discuss the potential molecular mechanisms for interplay of microtubules, actin and Rho GTPase signalling in cell polarization and motility. Recent evidence suggests that microtubules locally modulate the activity of Rho GTPases and, conversely, Rho GTPases might be responsible for the initial polarization of the microtubule cytoskeleton. Thus, microtubules might be part of a positive feedback mechanism that maintains the stable polarization of a directionally migrating cell.
Key words: Cell motility, Rho GTPases, Cytoskeleton, Microtubules, Actin
This article has been cited by other articles:
![]() |
L. Tang, J. Franca-Koh, Y. Xiong, M.-Y. Chen, Y. Long, R. M. Bickford, D. A. Knecht, P. A. Iglesias, and P. N. Devreotes tsunami, the Dictyostelium homolog of the Fused kinase, is required for polarization and chemotaxis Genes & Dev., August 15, 2008; 22(16): 2278 - 2290. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. J. Keller, F. Pampaloni, G. Lattanzi, and E. H. K. Stelzer Three-Dimensional Microtubule Behavior in Xenopus Egg Extracts Reveals Four Dynamic States and State-Dependent Elastic Properties Biophys. J., August 1, 2008; 95(3): 1474 - 1486. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. C. Padmos, M. H. J. Hillegers, E. M. Knijff, R. Vonk, A. Bouvy, F. J. T. Staal, D. de Ridder, R. W. Kupka, W. A. Nolen, and H. A. Drexhage A Discriminating Messenger RNA Signature for Bipolar Disorder Formed by an Aberrant Expression of Inflammatory Genes in Monocytes Arch Gen Psychiatry, April 1, 2008; 65(4): 395 - 407. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. O'Rourke, C. Ward, J. Worthington, J. McKenna, A. Valentine, T. Robson, D. G. Hirst, and S. R. McKeown Evaluation of the Antiangiogenic Potential of AQ4N Clin. Cancer Res., March 1, 2008; 14(5): 1502 - 1509. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Efimov, N. Schiefermeier, I. Grigoriev, M. C. Brown, C. E. Turner, J. V. Small, and I. Kaverina Paxillin-dependent stimulation of microtubule catastrophes at focal adhesion sites J. Cell Sci., January 15, 2008; 121(2): 196 - 204. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. E Fiedler, M. Bajpai, and D. W Carr Identification and Characterization of RHOA-Interacting Proteins in Bovine Spermatozoa Biol Reprod, January 1, 2008; 78(1): 184 - 192. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Goulimari, H. Knieling, U. Engel, and R. Grosse LARG and mDia1 Link G{alpha}12/13 to Cell Polarity and Microtubule Dynamics Mol. Biol. Cell, January 1, 2008; 19(1): 30 - 40. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Pacheco, A. Vieira-de-Abreu, R. N. Gomes, G. Barbosa-Lima, L. B. Wermelinger, C. M. Maya-Monteiro, A. R. Silva, M. T. Bozza, H. C. Castro-Faria-Neto, C. Bandeira-Melo, et al. Monocyte Chemoattractant Protein-1/CC Chemokine Ligand 2 Controls Microtubule-Driven Biogenesis and Leukotriene B4-Synthesizing Function of Macrophage Lipid Bodies Elicited by Innate Immune Response J. Immunol., December 15, 2007; 179(12): 8500 - 8508. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Mseka, J. R. Bamburg, and L. P. Cramer ADF/cofilin family proteins control formation of oriented actin-filament bundles in the cell body to trigger fibroblast polarization J. Cell Sci., December 15, 2007; 120(24): 4332 - 4344. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Motegi and G. Seydoux Revisiting the role of microtubules in C. elegans polarity J. Cell Biol., November 5, 2007; 179(3): 367 - 369. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Furlong, J. Crean, L. Thornton, R. O'Leary, M. Murphy, and F. Martin Dysregulated intracellular signaling impairs CTGF-stimulated responses in human mesangial cells exposed to high extracellular glucose Am J Physiol Renal Physiol, June 1, 2007; 292(6): F1691 - F1700. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Legrand-Poels, G. Kustermans, F. Bex, E. Kremmer, T. A. Kufer, and J. Piette Modulation of Nod2-dependent NF-{kappa}B signaling by the actin cytoskeleton J. Cell Sci., April 1, 2007; 120(7): 1299 - 1310. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. M. Bourzac, C. M. Botham, and K. Guillemin Helicobacter pylori CagA Induces AGS Cell Elongation through a Cell Retraction Defect That Is Independent of Cdc42, Rac1, and Arp2/3 Infect. Immun., March 1, 2007; 75(3): 1203 - 1213. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. E. Siegrist and C. Q. Doe Microtubule-induced cortical cell polarity Genes & Dev., March 1, 2007; 21(5): 483 - 496. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Mimori-Kiyosue, C. Matsui, H. Sasaki, and S. Tsukita Adenomatous polyposis coli (APC) protein regulates epithelial cell migration and morphogenesis via PDZ domain-based interactions with plasma membranes. Genes Cells, February 1, 2007; 12(2): 219 - 233. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. C. Dowdy, S. Jiang, X. C. Zhou, X. Hou, F. Jin, K. C. Podratz, and S.-W. Jiang Histone deacetylase inhibitors and paclitaxel cause synergistic effects on apoptosis and microtubule stabilization in papillary serous endometrial cancer cells. Mol. Cancer Ther., November 1, 2006; 5(11): 2767 - 2776. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Fojo Can mutations in gamma-actin modulate the toxicity of microtubule targeting agents? J Natl Cancer Inst, October 4, 2006; 98(19): 1345 - 1347. [Full Text] [PDF] |
||||
![]() |
K. Lawler, E. Foran, G. O'Sullivan, A. Long, and D. Kenny Mobility and invasiveness of metastatic esophageal cancer are potentiated by shear stress in a ROCK- and Ras-dependent manner Am J Physiol Cell Physiol, October 1, 2006; 291(4): C668 - C677. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. N.A. Bijman, G. P. van Nieuw Amerongen, N. Laurens, V. W.M. van Hinsbergh, and E. Boven Microtubule-targeting agents inhibit angiogenesis at subtoxic concentrations, a process associated with inhibition of Rac1 and Cdc42 activity and changes in the endothelial cytoskeleton. Mol. Cancer Ther., September 1, 2006; 5(9): 2348 - 2357. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. R. Cabrero, J. M. Serrador, O. Barreiro, M. Mittelbrunn, S. Naranjo-Suarez, N. Martin-Cofreces, M. Vicente-Manzanares, R. Mazitschek, J. E. Bradner, J. Avila, et al. Lymphocyte Chemotaxis Is Regulated by Histone Deacetylase 6, Independently of Its Deacetylase Activity Mol. Biol. Cell, August 1, 2006; 17(8): 3435 - 3445. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Van Keymeulen, K. Wong, Z. A. Knight, C. Govaerts, K. M. Hahn, K. M. Shokat, and H. R. Bourne To stabilize neutrophil polarity, PIP3 and Cdc42 augment RhoA activity at the back as well as signals at the front J. Cell Biol., July 31, 2006; 174(3): 437 - 445. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Lu, J. Murtagh, and E. L. Schwartz The Microtubule Binding Drug Laulimalide Inhibits Vascular Endothelial Growth Factor-Induced Human Endothelial Cell Migration and Is Synergistic when Combined with Docetaxel (Taxotere) Mol. Pharmacol., April 1, 2006; 69(4): 1207 - 1215. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. H. Brown, D. P. Del Re, and M. A. Sussman The Rac and Rho Hall of Fame: A Decade of Hypertrophic Signaling Hits Circ. Res., March 31, 2006; 98(6): 730 - 742. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. A. Minin, A. V. Kulik, F. K. Gyoeva, Y. Li, G. Goshima, and V. I. Gelfand Regulation of mitochondria distribution by RhoA and formins J. Cell Sci., February 15, 2006; 119(4): 659 - 670. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Janulevicius, J. van Pelt, and A. van Ooyen Compartment Volume Influences Microtubule Dynamic Instability: A Model Study Biophys. J., February 1, 2006; 90(3): 788 - 798. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Manna, D. Thrower, H. P. Miller, P. Curmi, and L. Wilson Stathmin Strongly Increases the Minus End Catastrophe Frequency and Induces Rapid Treadmilling of Bovine Brain Microtubules at Steady State in Vitro J. Biol. Chem., January 27, 2006; 281(4): 2071 - 2078. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Takino, M. Nakada, H. Miyamori, Y. Watanabe, T. Sato, D. Gantulga, K. Yoshioka, K. M. Yamada, and H. Sato JSAP1/JIP3 Cooperates with Focal Adhesion Kinase to Regulate c-Jun N-terminal Kinase and Cell Migration J. Biol. Chem., November 11, 2005; 280(45): 37772 - 37781. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Matenia, B. Griesshaber, X.-y. Li, A. Thiessen, C. Johne, J. Jiao, E. Mandelkow, and E.-M. Mandelkow PAK5 Kinase Is an Inhibitor of MARK/Par-1, Which Leads to Stable Microtubules and Dynamic Actin Mol. Biol. Cell, September 1, 2005; 16(9): 4410 - 4422. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Gorovoy, J. Niu, O. Bernard, J. Profirovic, R. Minshall, R. Neamu, and T. Voyno-Yasenetskaya LIM Kinase 1 Coordinates Microtubule Stability and Actin Polymerization in Human Endothelial Cells J. Biol. Chem., July 15, 2005; 280(28): 26533 - 26542. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Wittmann and C. M. Waterman-Storer Spatial regulation of CLASP affinity for microtubules by Rac1 and GSK3{beta} in migrating epithelial cells J. Cell Biol., June 20, 2005; 169(6): 929 - 939. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Xu, F. Wang, A. Van Keymeulen, M. Rentel, and H. R. Bourne Neutrophil microtubules suppress polarity and enhance directional migration PNAS, May 10, 2005; 102(19): 6884 - 6889. [Abstract] [Full Text] [PDF] |
||||
![]() |
J.-Y. Lang, H. Chen, J. Zhou, Y.-X. Zhang, X.-W. Zhang, M.-H. Li, L.-P. Lin, J.-S. Zhang, M. P. Waalkes, and J. Ding Antimetastatic Effect of Salvicine on Human Breast Cancer MDA-MB-435 Orthotopic Xenograft Is Closely Related to Rho-Dependent Pathway Clin. Cancer Res., May 1, 2005; 11(9): 3455 - 3464. [Abstract] [Full Text] [PDF] |
||||
![]() |
S.-O. Yoon, S. Shin, and A. M. Mercurio Hypoxia Stimulates Carcinoma Invasion by Stabilizing Microtubules and Promoting the Rab11 Trafficking of the {alpha}6{beta}4 Integrin Cancer Res., April 1, 2005; 65(7): 2761 - 2769. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Fujita, S. Fukuhara, A. Sakurai, A. Yamagishi, Y. Kamioka, Y. Nakaoka, M. Masuda, and N. Mochizuki Local Activation of Rap1 Contributes to Directional Vascular Endothelial Cell Migration Accompanied by Extension of Microtubules on Which RAPL, a Rap1-associating Molecule, Localizes J. Biol. Chem., February 11, 2005; 280(6): 5022 - 5031. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Endo, V. Wolf, K. Muraiso, K. Kamijo, L. Soon, A. Uren, M. Barshishat-Kupper, and J. S. Rubin Wnt-3a-dependent Cell Motility Involves RhoA Activation and Is Specifically Regulated by Dishevelled-2 J. Biol. Chem., January 7, 2005; 280(1): 777 - 786. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. P. Kole, Y. Tseng, I. Jiang, J. L. Katz, and D. Wirtz Intracellular Mechanics of Migrating Fibroblasts Mol. Biol. Cell, January 1, 2005; 16(1): 328 - 338. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. P. Desai, A. M. Aryal, B. Ceacareanu, A. Hassid, and C. M. Waters RhoA and Rac1 are both required for efficient wound closure of airway epithelial cells Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1134 - L1144. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. H. Modarressi, M. Cheng, H. A. Tarnasky, N. Lamarche-Vane, D. G. de Rooij, Y. Ruan, and F. A. van der Hoorn A Novel Testicular RhoGAP-Domain Protein Induces Apoptosis Biol Reprod, December 1, 2004; 71(6): 1980 - 1990. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Larsen, E. Tufvesson, J. Malmstrom, M. Morgelin, M. Wildt, A. Andersson, A. Lindstrom, A. Malmstrom, C.-G. Lofdahl, G. Marko-Varga, et al. Presence of Activated Mobile Fibroblasts in Bronchoalveolar Lavage from Patients with Mild Asthma Am. J. Respir. Crit. Care Med., November 15, 2004; 170(10): 1049 - 1056. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. L. Miller, Y. Wang, M. S. Mooseker, and A. J. Koleske The Abl-related gene (Arg) requires its F-actin-microtubule cross-linking activity to regulate lamellipodial dynamics during fibroblast adhesion J. Cell Biol., May 10, 2004; 165(3): 407 - 419. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. I. Lacayo and J. A. Theriot Listeria monocytogenes Actin-based Motility Varies Depending on Subcellular Location: A Kinematic Probe for Cytoarchitecture Mol. Biol. Cell, May 1, 2004; 15(5): 2164 - 2175. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. T. Zenke, M. Krendel, C. DerMardirossian, C. C. King, B. P. Bohl, and G. M. Bokoch p21-activated Kinase 1 Phosphorylates and Regulates 14-3-3 Binding to GEF-H1, a Microtubule-localized Rho Exchange Factor J. Biol. Chem., April 30, 2004; 279(18): 18392 - 18400. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Ban, Y. Irino, K. Fukami, and H. Tanaka Human Mitotic Spindle-associated Protein PRC1 Inhibits MgcRacGAP Activity toward Cdc42 during the Metaphase J. Biol. Chem., April 16, 2004; 279(16): 16394 - 16402. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. M. Grimsley, J. M. Kinchen, A.-C. Tosello-Trampont, E. Brugnera, L. B. Haney, M. Lu, Q. Chen, D. Klingele, M. O. Hengartner, and K. S. Ravichandran Dock180 and ELMO1 Proteins Cooperate to Promote Evolutionarily Conserved Rac-dependent Cell Migration J. Biol. Chem., February 13, 2004; 279(7): 6087 - 6097. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Wittmann, G. M. Bokoch, and C. M. Waterman-Storer Regulation of Microtubule Destabilizing Activity of Op18/Stathmin Downstream of Rac1 J. Biol. Chem., February 13, 2004; 279(7): 6196 - 6203. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Burgstaller and M. Gimona Actin cytoskeleton remodelling via local inhibition of contractility at discrete microdomains J. Cell Sci., January 15, 2004; 117(2): 223 - 231. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Shang, Y. T. Zhou, and B. C. Low Concerted Regulation of Cell Dynamics by BNIP-2 and Cdc42GAP Homology/Sec14p-like, Proline-rich, and GTPase-activating Protein Domains of a Novel Rho GTPase-activating Protein, BPGAP1 J. Biol. Chem., November 14, 2003; 278(46): 45903 - 45914. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. M. Scaife, D. Job, and W. Y. Langdon Rapid Microtubule-dependent Induction of Neurite-like Extensions in NIH 3T3 Fibroblasts by Inhibition of ROCK and Cbl Mol. Biol. Cell, November 1, 2003; 14(11): 4605 - 4617. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. M. Razzaq, R. Bass, D. J. Vines, F. Werner, S. A. Whawell, and V. Ellis Functional Regulation of Tissue Plasminogen Activator on the Surface of Vascular Smooth Muscle Cells by the Type-II Transmembrane Protein p63 (CKAP4) J. Biol. Chem., October 24, 2003; 278(43): 42679 - 42685. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Dehmelt, F. M. Smart, R. S. Ozer, and S. Halpain The Role of Microtubule-Associated Protein 2c in the Reorganization of Microtubules and Lamellipodia during Neurite Initiation J. Neurosci., October 22, 2003; 23(29): 9479 - 9490. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Malorni, M. G. Quaranta, E. Straface, L. Falzano, A. Fabbri, M. Viora, and C. Fiorentini The Rac-Activating Toxin Cytotoxic Necrotizing Factor 1 Oversees NK Cell-Mediated Activity by Regulating the Actin/Microtubule Interplay J. Immunol., October 15, 2003; 171(8): 4195 - 4202. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. S. Kholmanskikh, J. S. Dobrin, A. Wynshaw-Boris, P. C. Letourneau, and M. E. Ross Disregulated RhoGTPases and Actin Cytoskeleton Contribute to the Migration Defect in Lis1-Deficient Neurons J. Neurosci., September 24, 2003; 23(25): 8673 - 8681. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Burakov, E. Nadezhdina, B. Slepchenko, and V. Rodionov Centrosome positioning in interphase cells J. Cell Biol., September 15, 2003; 162(6): 963 - 969. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Mimori-Kiyosue and S. Tsukita "Search-and-Capture" of Microtubules through Plus-End-Binding Proteins (+TIPs) J. Biochem., September 1, 2003; 134(3): 321 - 326. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Kogata, M. Masuda, Y. Kamioka, A. Yamagishi, A. Endo, M. Okada, and N. Mochizuki Identification of Fer Tyrosine Kinase Localized on Microtubules as a Platelet Endothelial Cell Adhesion Molecule-1 Phosphorylating Kinase in Vascular Endothelial Cells Mol. Biol. Cell, September 1, 2003; 14(9): 3553 - 3564. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Kelkar, M.-H. Delmotte, C. R. Weston, T. Barrett, B. J. Sheppard, R. A. Flavell, and R. J. Davis Morphogenesis of the telencephalic commissure requires scaffold protein JNK-interacting protein 3 (JIP3) PNAS, August 19, 2003; 100(17): 9843 - 9848. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Silva, A. Beckedorf, and E. Bieberich Osteoblast-derived Oxysterol Is a Migration-inducing Factor for Human Breast Cancer Cells J. Biol. Chem., July 3, 2003; 278(28): 25376 - 25385. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. N. Fass and D. J. Odde Tensile Force-Dependent Neurite Elicitation via Anti-{beta}1 Integrin Antibody-Coated Magnetic Beads Biophys. J., July 1, 2003; 85(1): 623 - 636. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Lamorte, S. Rodrigues, V. Sangwan, C. E. Turner, and M. Park Crk Associates with a Multimolecular Paxillin/GIT2/{beta}-PIX Complex and Promotes Rac-dependent Relocalization of Paxillin to Focal Contacts Mol. Biol. Cell, July 1, 2003; 14(7): 2818 - 2831. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M. Summy, Y. Qian, B.-H. Jiang, A. Guappone-Koay, A. Gatesman, X. Shi, and D. C. Flynn The SH4-Unique-SH3-SH2 domains dictate specificity in signaling that differentiate c-Yes from c-Src J. Cell Sci., June 15, 2003; 116(12): 2585 - 2598. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. Krylyshkina, K. I. Anderson, I. Kaverina, I. Upmann, D. J. Manstein, J. V. Small, and D. K. Toomre Nanometer targeting of microtubules to focal adhesions J. Cell Biol., June 9, 2003; 161(5): 853 - 859. [Abstract] [Full Text] [PDF] |
||||