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.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 6 February 2004:
Vol. 303. no. 5659, pp. 836 - 839
DOI: 10.1126/science.1091325
Prev | Table of Contents | Next

Reports

Localized Stabilization of Microtubules by Integrin- and FAK-Facilitated Rho Signaling

Alexander F. Palazzo,1 Christina H. Eng,1,2 David D. Schlaepfer,4 Eugene E. Marcantonio,1,3 Gregg G. Gundersen1,3*

Microtubule (MT) stabilization is regulated by the small guanosine triphosphate (GTP)–binding protein Rho and its effector, mammalian homolog of Diaphanous (mDia), in migrating cells, but factors responsible for localized stabilization at the leading edge are unknown. We report that integrin-mediated activation of focal adhesion kinase (FAK) at the leading edge is required for MT stabilization by the Rho-mDia signaling pathway in mouse fibroblasts. MT stabilization also involved FAK-regulated localization of a lipid raft marker, ganglioside GM1, to the leading edge. The integrin-FAK signaling pathway may facilitate Rho-mDia signaling through GM1, or through a specialized membrane domain containing GM1, to stabilize MTs in the leading edge of migrating cells.

1 Department of Anatomy and Cell Biology, Columbia University, New York, NY 10032, USA.
2 Integrated Program in Cellular, Molecular, and Biophysical Studies, Columbia University, New York, NY 10032, USA.
3 Department of Pathology, Columbia University, New York, NY 10032, USA.
4 Department of Immunology, Scripps Research Institute, La Jolla, CA 92307, USA.

* To whom correspondence should be addressed. E-mail: ggg1{at}columbia.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Definition of Arabidopsis Sterol-rich Membrane Microdomains by Differential Treatment with Methyl-{beta}-cyclodextrin and Quantitative Proteomics.
S. Kierszniowska, B. Seiwert, and W. X. Schulze (2009)
Mol. Cell. Proteomics 8, 612-623
   Abstract »    Full Text »    PDF »
Activation of Signal Transducers and Activators of Transcription 3 and Focal Adhesion Kinase by Stromal Cell-Derived Factor 1 Is Required for Migration of Human Mesenchymal Stem Cells in Response to Tumor Cell-Conditioned Medium.
H. Gao, W. Priebe, J. Glod, and D. Banerjee (2009)
Stem Cells 27, 857-865
   Abstract »    Full Text »    PDF »
Apolipoprotein(a), through Its Strong Lysine-binding Site in KIV10, Mediates Increased Endothelial Cell Contraction and Permeability via a Rho/Rho Kinase/MYPT1-dependent Pathway.
T. Cho, Y. Jung, and M. L. Koschinsky (2008)
J. Biol. Chem. 283, 30503-30512
   Abstract »    Full Text »    PDF »
Formin-Dependent Synaptic Growth: Evidence That Dlar Signals via Diaphanous to Modulate Synaptic Actin and Dynamic Pioneer Microtubules.
C. Pawson, B. A. Eaton, and G. W. Davis (2008)
J. Neurosci. 28, 11111-11123
   Abstract »    Full Text »    PDF »
Regulation of RhoA-dependent ROCKII activation by Shp2.
H.-H. Lee and Z.-F. Chang (2008)
J. Cell Biol. 181, 999-1012
   Abstract »    Full Text »    PDF »
Vesicles and actin are targeted to the cleavage furrow via furrow microtubules and the central spindle.
R. Albertson, J. Cao, T.-s. Hsieh, and W. Sullivan (2008)
J. Cell Biol. 181, 777-790
   Abstract »    Full Text »    PDF »
Mechanotransduction - a field pulling together?.
C. S. Chen (2008)
J. Cell Sci. 121, 3285-3292
   Abstract »    Full Text »    PDF »
The formin mDia2 stabilizes microtubules independently of its actin nucleation activity.
F. Bartolini, J. B. Moseley, J. Schmoranzer, L. Cassimeris, B. L. Goode, and G. G. Gundersen (2008)
J. Cell Biol. 181, 523-536
   Abstract »    Full Text »    PDF »
Stathmin Activity Influences Sarcoma Cell Shape, Motility, and Metastatic Potential.
B. Belletti, M. S. Nicoloso, M. Schiappacassi, S. Berton, F. Lovat, K. Wolf, V. Canzonieri, S. D'Andrea, A. Zucchetto, P. Friedl, et al. (2008)
Mol. Biol. Cell 19, 2003-2013
   Abstract »    Full Text »    PDF »
FAK, PDZ-RhoGEF and ROCKII cooperate to regulate adhesion movement and trailing-edge retraction in fibroblasts.
M. P. Iwanicki, T. Vomastek, R. W. Tilghman, K. H. Martin, J. Banerjee, P. B. Wedegaertner, and J. T. Parsons (2008)
J. Cell Sci. 121, 895-905
   Abstract »    Full Text »    PDF »
Mice Lacking Histone Deacetylase 6 Have Hyperacetylated Tubulin but Are Viable and Develop Normally.
Y. Zhang, S. Kwon, T. Yamaguchi, F. Cubizolles, S. Rousseaux, M. Kneissel, C. Cao, N. Li, H.-L. Cheng, K. Chua, et al. (2008)
Mol. Cell. Biol. 28, 1688-1701
   Abstract »    Full Text »    PDF »
Dynamic interplay between nitration and phosphorylation of tubulin cofactor B in the control of microtubule dynamics.
S. K. Rayala, E. Martin, I. G. Sharina, P. R. Molli, X. Wang, R. Jacobson, F. Murad, and R. Kumar (2007)
PNAS 104, 19470-19475
   Abstract »    Full Text »    PDF »
Wild-Type NRas and KRas Perform Distinct Functions during Transformation.
P. P. Fotiadou, C. Takahashi, H. N. Rajabi, and M. E. Ewen (2007)
Mol. Cell. Biol. 27, 6742-6755
   Abstract »    Full Text »    PDF »
Mannheimia haemolytica Leukotoxin Binds to Lipid Rafts in Bovine Lymphoblastoid Cells and Is Internalized in a Dynamin-2- and Clathrin-Dependent Manner.
D. N. Atapattu and C. J. Czuprynski (2007)
Infect. Immun. 75, 4719-4727
   Abstract »    Full Text »    PDF »
mDia2 regulates actin and focal adhesion dynamics and organization in the lamella for efficient epithelial cell migration.
S. L. Gupton, K. Eisenmann, A. S. Alberts, and C. M. Waterman-Storer (2007)
J. Cell Sci. 120, 3475-3487
   Abstract »    Full Text »    PDF »
Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2 / mice.
H. Gil-Henn, O. Destaing, N. A. Sims, K. Aoki, N. Alles, L. Neff, A. Sanjay, A. Bruzzaniti, P. De Camilli, R. Baron, et al. (2007)
J. Cell Biol. 178, 1053-1064
   Abstract »    Full Text »    PDF »
Lipid Rafts of Primary Endothelial Cells Are Essential for Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8-Induced Phosphatidylinositol 3-Kinase and RhoA-GTPases Critical for Microtubule Dynamics and Nuclear Delivery of Viral DNA but Dispensable for Binding and Entry.
H. Raghu, N. Sharma-Walia, M. V. Veettil, S. Sadagopan, A. Caballero, R. Sivakumar, L. Varga, V. Bottero, and B. Chandran (2007)
J. Virol. 81, 7941-7959
   Abstract »    Full Text »    PDF »
HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions.
A. D.-A. Tran, T. P. Marmo, A. A. Salam, S. Che, E. Finkelstein, R. Kabarriti, H. S. Xenias, R. Mazitschek, C. Hubbert, Y. Kawaguchi, et al. (2007)
J. Cell Sci. 120, 1469-1479
   Abstract »    Full Text »    PDF »
Neuroendocrine Plasticity in the Anterior Pituitary: Gonadotropin-Releasing Hormone-Mediated Movement in Vitro and in Vivo.
A. M. Navratil, J. G. Knoll, J. D. Whitesell, S. A. Tobet, and C. M. Clay (2007)
Endocrinology 148, 1736-1744
   Abstract »    Full Text »    PDF »
The PI3K-Akt pathway promotes microtubule stabilization in migrating fibroblasts.
K. Onishi, M. Higuchi, T. Asakura, N. Masuyama, and Y. Gotoh (2007)
Genes Cells 12, 535-546
   Abstract »    Full Text »    PDF »
Role of the Lipopolysaccharide-CD14 Complex for the Activity of Hemolysin from Uropathogenic Escherichia coli.
L. E. Mansson, P. Kjall, S. Pellett, G. Nagy, R. A. Welch, F. Backhed, T. Frisan, and A. Richter-Dahlfors (2007)
Infect. Immun. 75, 997-1004
   Abstract »    Full Text »    PDF »
Adherens junction-associated protein distribution differs in smooth muscle tissue and acutely isolated cells.
T. J. Eddinger, J. D. Schiebout, and D. R. Swartz (2007)
Am J Physiol Gastrointest Liver Physiol 292, G684-G697
   Abstract »    Full Text »    PDF »
From the Cover: Anisotropy of cell adhesive microenvironment governs cell internal organization and orientation of polarity.
M. Thery, V. Racine, M. Piel, A. Pepin, A. Dimitrov, Y. Chen, J.-B. Sibarita, and M. Bornens (2006)
PNAS 103, 19771-19776
   Abstract »    Full Text »    PDF »
RhoA-GTPase Facilitates Entry of Kaposi's Sarcoma-Associated Herpesvirus into Adherent Target Cells in a Src-Dependent Manner.
M. V. Veettil, N. Sharma-Walia, S. Sadagopan, H. Raghu, R. Sivakumar, P. P. Naranatt, and B. Chandran (2006)
J. Virol. 80, 11432-11446
   Abstract »    Full Text »    PDF »
The Formin mDia Regulates GSK3beta through Novel PKCs to Promote Microtubule Stabilization but Not MTOC Reorientation in Migrating Fibroblasts.
C. H. Eng, T. M. Huckaba, and G. G. Gundersen (2006)
Mol. Biol. Cell 17, 5004-5016
   Abstract »    Full Text »    PDF »
Usher syndrome: molecular links of pathogenesis, proteins and pathways.
H. Kremer, E. van Wijk, T. Marker, U. Wolfrum, and R. Roepman (2006)
Hum. Mol. Genet. 15, R262-R270
   Abstract »    Full Text »    PDF »
Initiation of Attachment and Generation of Mature Focal Adhesions by Integrin-containing Filopodia in Cell Spreading.
M. A. Partridge and E. E. Marcantonio (2006)
Mol. Biol. Cell 17, 4237-4248
   Abstract »    Full Text »    PDF »
Integrin traffic..
T. Pellinen and J. Ivaska (2006)
J. Cell Sci. 119, 3723-3731
   Abstract »    Full Text »    PDF »
Lymphocyte Chemotaxis Is Regulated by Histone Deacetylase 6, Independently of Its Deacetylase Activity.
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. (2006)
Mol. Biol. Cell 17, 3435-3445
   Abstract »    Full Text »    PDF »
Infection with Replication-deficient Adenovirus Induces Changes in the Dynamic Instability of Host Cell Microtubules.
J. C. Warren, A. Rutkowski, and L. Cassimeris (2006)
Mol. Biol. Cell 17, 3557-3568
   Abstract »    Full Text »    PDF »
Distinct Mechanisms of Clathrin-independent Endocytosis Have Unique Sphingolipid Requirements.
Z.-J. Cheng, R. D. Singh, D. K. Sharma, E. L. Holicky, K. Hanada, D. L. Marks, and R. E. Pagano (2006)
Mol. Biol. Cell 17, 3197-3210
   Abstract »    Full Text »    PDF »
Shear Stress Regulates Forward and Reverse Planar Cell Polarity of Vascular Endothelium In Vivo and In Vitro.
S. McCue, D. Dajnowiec, F. Xu, M. Zhang, M. R. Jackson, and B. L. Langille (2006)
Circ. Res. 98, 939-946
   Abstract »    Full Text »    PDF »
Displacement of the {beta} cytoplasmic domain recovers focal adhesion formation, cytoskeletal organization and motility in swapped integrin chimeras.
M. A. Partridge, F. S. David, and E. E. Marcantonio (2006)
J. Cell Sci. 119, 1175-1183
   Abstract »    Full Text »    PDF »
Role of non-raft cholesterol in lymphocytic choriomeningitis virus infection via {alpha}-dystroglycan..
W. A. Shah, H. Peng, and S. Carbonetto (2006)
J. Gen. Virol. 87, 673-678
   Abstract »    Full Text »    PDF »
Regulation of mitochondria distribution by RhoA and formins.
A. A. Minin, A. V. Kulik, F. K. Gyoeva, Y. Li, G. Goshima, and V. I. Gelfand (2006)
J. Cell Sci. 119, 659-670
   Abstract »    Full Text »    PDF »
P21-activated kinase 1: convergence point in PDGF- and LPA-stimulated collagen matrix contraction by human fibroblasts.
S. Rhee and F. Grinnell (2006)
J. Cell Biol. 172, 423-432
   Abstract »    Full Text »    PDF »
Stat3 regulates microtubules by antagonizing the depolymerization activity of stathmin.
D. C. H. Ng, B. H. Lin, C. P. Lim, G. Huang, T. Zhang, V. Poli, and X. Cao (2006)
J. Cell Biol. 172, 245-257
   Abstract »    Full Text »    PDF »
Smooth muscle adherens junctions associated proteins are stable at the cell periphery during relaxation and activation.
T. J. Eddinger, J. D. Schiebout, and D. R. Swartz (2005)
Am J Physiol Cell Physiol 289, C1379-C1387
   Abstract »    Full Text »    PDF »
JSAP1/JIP3 Cooperates with Focal Adhesion Kinase to Regulate c-Jun N-terminal Kinase and Cell Migration.
T. Takino, M. Nakada, H. Miyamori, Y. Watanabe, T. Sato, D. Gantulga, K. Yoshioka, K. M. Yamada, and H. Sato (2005)
J. Biol. Chem. 280, 37772-37781
   Abstract »    Full Text »    PDF »
From the Cover: p600, a unique protein required for membrane morphogenesis and cell survival.
Y. Nakatani, H. Konishi, A. Vassilev, H. Kurooka, K. Ishiguro, J.-i. Sawada, T. Ikura, S. J. Korsmeyer, J. Qin, and A. M. Herlitz (2005)
PNAS 102, 15093-15098
   Abstract »    Full Text »    PDF »
The Glycosphingolipid, Lactosylceramide, Regulates {beta}1-Integrin Clustering and Endocytosis.
D. K. Sharma, J. C. Brown, Z. Cheng, E. L. Holicky, D. L. Marks, and R. E. Pagano (2005)
Cancer Res. 65, 8233-8241
   Abstract »    Full Text »    PDF »
Focal Adhesion Kinase Plays a Pivotal Role in Herpes Simplex Virus Entry.
N. Cheshenko, W. Liu, L. M. Satlin, and B. C. Herold (2005)
J. Biol. Chem. 280, 31116-31125
   Abstract »    Full Text »    PDF »
{alpha}v{beta}3-integrin-dependent activation of focal adhesion kinase mediates NF-{kappa}B activation and motogenic activity by HIV-1 Tat in endothelial cells.
C. Urbinati, A. Bugatti, M. Giacca, D. Schlaepfer, M. Presta, and M. Rusnati (2005)
J. Cell Sci. 118, 3949-3958
   Abstract »    Full Text »    PDF »
The Rho GTP exchange factor Lfc promotes spindle assembly in early mitosis.
C. J. Bakal, D. Finan, J. LaRose, C. D. Wells, G. Gish, S. Kulkarni, P. DeSepulveda, A. Wilde, and R. Rottapel (2005)
PNAS 102, 9529-9534
   Abstract »    Full Text »    PDF »
Fhos2, a novel formin-related actin-organizing protein, probably associates with the nestin intermediate filament.
H. Kanaya, R. Takeya, K. Takeuchi, N. Watanabe, N. Jing, and H. Sumimoto (2005)
Genes Cells 10, 665-678
   Abstract »    Full Text »    PDF »
G Protein-coupled Receptor Activation Rapidly Stimulates Focal Adhesion Kinase Phosphorylation at Ser-843: MEDIATION BY Ca2+, CALMODULIN, AND Ca2+/CALMODULIN-DEPENDENT KINASE II.
R. S. Fan, R. O. Jacamo, X. Jiang, J. Sinnett-Smith, and E. Rozengurt (2005)
J. Biol. Chem. 280, 24212-24220
   Abstract »    Full Text »    PDF »
Spatial regulation of CLASP affinity for microtubules by Rac1 and GSK3{beta} in migrating epithelial cells.
T. Wittmann and C. M. Waterman-Storer (2005)
J. Cell Biol. 169, 929-939
   Abstract »    Full Text »    PDF »
The MEK1 Scaffolding Protein MP1 Regulates Cell Spreading by Integrating PAK1 and Rho Signals.
A. Pullikuth, E. McKinnon, H.-J. Schaeffer, and A. D. Catling (2005)
Mol. Cell. Biol. 25, 5119-5133
   Abstract »    Full Text »    PDF »
RhoB regulates endosome transport by promoting actin assembly on endosomal membranes through Dia1.
M. Fernandez-Borja, L. Janssen, D. Verwoerd, P. Hordijk, and J. Neefjes (2005)
J. Cell Sci. 118, 2661-2670
   Abstract »    Full Text »    PDF »
PI(4,5)P2-dependent microdomain assemblies capture microtubules to promote and control leading edge motility.
T. Golub and P. Caroni (2005)
J. Cell Biol. 169, 151-165
   Abstract »    Full Text »    PDF »
Integrin Engagement Differentially Modulates Epithelial Cell Motility by RhoA/ROCK and PAK1.
H. Zhou and R. H. Kramer (2005)
J. Biol. Chem. 280, 10624-10635
   Abstract »    Full Text »    PDF »
CXC Chemokine Ligand 12-Induced Focal Adhesion Kinase Activation and Segregation into Membrane Domains Is Modulated by Regulator of G Protein Signaling 1 in Pro-B Cells.
Y. Le, M. Honczarenko, A. M. Glodek, D. K. Ho, and L. E. Silberstein (2005)
J. Immunol. 174, 2582-2590
   Abstract »    Full Text »    PDF »
Persistent Borna Disease Virus Infection Confers Instability of HSP70 mRNA in Glial Cells during Heat Stress.
M. Yamashita, W. Kamitani, H. Yanai, N. Ohtaki, Y. Watanabe, B.-J. Lee, S. Tsuji, K. Ikuta, and K. Tomonaga (2005)
J. Virol. 79, 2033-2041
   Abstract »    Full Text »    PDF »
Molecular Control of Cytoskeletal Mechanics by Hemodynamic Forces.
B. P. Helmke (2005)
Physiology 20, 43-53
   Abstract »    Full Text »    PDF »
Incorporation of CXCR4 into membrane lipid rafts primes homing-related responses of hematopoietic stem/progenitor cells to an SDF-1 gradient.
M. Wysoczynski, R. Reca, J. Ratajczak, M. Kucia, N. Shirvaikar, M. Honczarenko, M. Mills, J. Wanzeck, A. Janowska-Wieczorek, and M. Z. Ratajczak (2005)
Blood 105, 40-48
   Abstract »    Full Text »    PDF »
Novel role of microtubules in thrombin-induced endothelial barrier dysfunction.
A. A. BIRUKOVA, K. G. BIRUKOV, K. SMUROVA, D. ADYSHEV, K. KAIBUCHI, I. ALIEVA, J. G. N. GARCIA, and A. D. VERIN (2004)
FASEB J 18, 1879-1890
   Abstract »    Full Text »    PDF »
Coordinating cytoskeletal tracks to polarize cellular movements.
A. Kodama, T. Lechler, and E. Fuchs (2004)
J. Cell Biol. 167, 203-207
   Abstract »    Full Text »    PDF »
Paxillin: Adapting to Change.
M. C. Brown and C. E. Turner (2004)
Physiol Rev 84, 1315-1339
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)