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Science 302 (5642): 103-106

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

Talin Binding to Integrin ß Tails: A Final Common Step in Integrin Activation

Seiji Tadokoro,1 Sanford J. Shattil,1 Koji Eto,1 Vera Tai,1 Robert C. Liddington,2 José M. de Pereda,2 Mark H. Ginsberg,1* David A. Calderwood1

Abstract: Control of integrin affinity for ligands (integrin activation) is essential for normal cell adhesion, migration, and assembly of an extracellular matrix. Integrin activation is usually mediated through the integrin ß subunit cytoplasmic tail and can be regulated by many different biochemical signaling pathways. We report that specific binding of the cytoskeletal protein talin to integrin ß subunit cytoplasmic tails leads to the conformational rearrangements of integrin extracellular domains that increase their affinity. Thus, regulated binding of talin to integrin ß tails is a final common element of cellular signaling cascades that control integrin activation.

1 Department of Cell Biology, The Scripps Research Institute, The Burnham Institute, La Jolla, CA 92037, USA.
2 Program in Cell Adhesion, The Burnham Institute, La Jolla, CA 92037, USA.

* To whom correspondence should be addressed. E-mail: ginsberg{at}

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New PI(4,5)P2- and membrane proximal integrin-binding motifs in the talin head control {beta}3-integrin clustering.
F. Saltel, E. Mortier, V. P. Hytonen, M.-C. Jacquier, P. Zimmermann, V. Vogel, W. Liu, and B. Wehrle-Haller (2009)
J. Cell Biol. 187, 715-731
   Abstract »    Full Text »    PDF »
The structure of an integrin/talin complex reveals the basis of inside-out signal transduction.
N. J. Anthis, K. L. Wegener, F. Ye, C. Kim, B. T. Goult, E. D. Lowe, I. Vakonakis, N. Bate, D. R. Critchley, M. H. Ginsberg, et al. (2009)
EMBO J. 28, 3623-3632
   Abstract »    Full Text »    PDF »
Talin 1 and 2 are required for myoblast fusion, sarcomere assembly and the maintenance of myotendinous junctions.
F. J. Conti, S. J. Monkley, M. R. Wood, D. R. Critchley, and U. Muller (2009)
Development 136, 3597-3606
   Abstract »    Full Text »    PDF »
Clustering of {alpha}5{beta}1 integrins determines adhesion strength whereas {alpha}v{beta}3 and talin enable mechanotransduction.
P. Roca-Cusachs, N. C. Gauthier, A. del Rio, and M. P. Sheetz (2009)
PNAS 106, 16245-16250
   Abstract »    Full Text »    PDF »
Liprin-{alpha}1 promotes cell spreading on the extracellular matrix by affecting the distribution of activated integrins.
C. Asperti, V. Astro, A. Totaro, S. Paris, and I. de Curtis (2009)
J. Cell Sci. 122, 3225-3232
   Abstract »    Full Text »    PDF »
Dynamic changes in Rap1 activity are required for cell retraction and spreading during mitosis.
V. T. Dao, A. G. Dupuy, O. Gavet, E. Caron, and J. de Gunzburg (2009)
J. Cell Sci. 122, 2996-3004
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SLP-76-ADAP adaptor module regulates LFA-1 mediated costimulation and T cell motility.
H. Wang, B. Wei, G. Bismuth, and C. E. Rudd (2009)
PNAS 106, 12436-12441
   Abstract »    Full Text »    PDF »
Quantitative proteomics identifies a Dab2/integrin module regulating cell migration.
A. Teckchandani, N. Toida, J. Goodchild, C. Henderson, J. Watts, B. Wollscheid, and J. A. Cooper (2009)
J. Cell Biol. 186, 99-111
   Abstract »    Full Text »    PDF »
Cytohesin-1 controls the activation of RhoA and modulates integrin-dependent adhesion and migration of dendritic cells.
T. Quast, B. Tappertzhofen, C. Schild, J. Grell, N. Czeloth, R. Forster, R. Alon, L. Fraemohs, K. Dreck, C. Weber, et al. (2009)
Blood 113, 5801-5810
   Abstract »    Full Text »    PDF »
The Structure of an Interdomain Complex That Regulates Talin Activity.
B. T. Goult, N. Bate, N. J. Anthis, K. L. Wegener, A. R. Gingras, B. Patel, I. L. Barsukov, I. D. Campbell, G. C. K. Roberts, and D. R. Critchley (2009)
J. Biol. Chem. 284, 15097-15106
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Integrin-linked kinase associated with integrin activation.
S. Honda, H. Shirotani-Ikejima, S. Tadokoro, Y. Maeda, T. Kinoshita, Y. Tomiyama, and T. Miyata (2009)
Blood 113, 5304-5313
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The Tail of Integrins, Talin, and Kindlins.
M. Moser, K. R. Legate, R. Zent, and R. Fassler (2009)
Science 324, 895-899
   Abstract »    Full Text »    PDF »
Control of High Affinity Interactions in the Talin C Terminus: HOW TALIN DOMAINS COORDINATE PROTEIN DYNAMICS IN CELL ADHESIONS.
M. Himmel, A. Ritter, S. Rothemund, B. V. Pauling, K. Rottner, A. R. Gingras, and W. H. Ziegler (2009)
J. Biol. Chem. 284, 13832-13842
   Abstract »    Full Text »    PDF »
Interactions of platelet integrin {alpha}IIb and {beta}3 transmembrane domains in mammalian cell membranes and their role in integrin activation.
C. Kim, T.-L. Lau, T. S. Ulmer, and M. H. Ginsberg (2009)
Blood 113, 4747-4753
   Abstract »    Full Text »    PDF »
LAD-1/variant syndrome is caused by mutations in FERMT3.
T. W. Kuijpers, E. van de Vijver, M. A. J. Weterman, M. de Boer, A. T. J. Tool, T. K. van den Berg, M. Moser, M. E. Jakobs, K. Seeger, O. Sanal, et al. (2009)
Blood 113, 4740-4746
   Abstract »    Full Text »    PDF »
Mst1 controls lymphocyte trafficking and interstitial motility within lymph nodes.
K. Katagiri, T. Katakai, Y. Ebisuno, Y. Ueda, T. Okada, and T. Kinashi (2009)
EMBO J. 28, 1319-1331
   Abstract »    Full Text »    PDF »

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