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Focal Contacts (Focal adhesions)

Page updated 19/2/03

Focal contacts are adhesions by which cell attach to the underlying substrate. A large number of specific proteins are known to be concentrated at focal contacts, these are usually structural and cytoskeletal proteins but many are also signalling molecules (Sastry & Burridge, 2000).

Cell-cell adherens   

Figure 1.  The main structural players at the Focal Contact.  The trans-membranous b-integrin binds talin and a-actinin which both then bind F-actin and vinculin.  The picture is further complicated by the fact that many of these proteins also bind and are regulated by PI lipids.
Protein Function References
ASAP1   Oda et al, 2003;
CrkL An SH2 and SH3 adapter protein  
ERK/MAP kinase   Fincham et al, 2000;
FAK Focal adhesion kinase   
Integrin A family of trans-membranous adhesions molecules  
MEKK1 A mitogen-activated protein kinase (binds FAK) Yujiri et al, 2003
Syndecan   Longley et al, 1999;
Tes   Coutts et al, 2003;
Zyxin   Nix et al, 1997;
Table 1   Focal Contact associated proteins

Microtubule Signalling to Focal Contacts

Migrating cells must make adhesions at the front end and break these adhesions as they become redundant at the rear. 


Burridge, K., Chrzanowska-Wodnicka, M. & Zhong, C. (1997) Focal adhesion assembly. Trends Cell Biol. 7, 342-347.

Coutts, A. S., MacKenzie, E., Griffith, E. & Black, D. M. (2003) TES is a novel focal adhesion protein with a role in cell spreading. J Cell Sci. 116, 897-906.

DePasquale, J. A. & Izzard, C. S. (1987) Evidence for an actin-containing cytoplasmic precursor of the focal contact and the timing of incorporation of vinculin at the focal contact. J.Cell Biol. 105, 2803-2809.

DePasquale, J. A. & Izzard, C. S. (1991) Accumulation of talin in nodes at the edge of the lammellipodium and separate incorporation into adhesion plaques at focal contacts in fibroblasts. J.Cell Biol. 113, 1351-1359.

Enomoto, T. (1996) Microtubule disruption induces the formation of actin stress fibers and focal adhesions in cultured cells: possible involvement of the rho signal cascade. Cell Sruct.Funct. 21, 317-326.

Fincham, V. J., Chudleigh, A. & Frame, M. C. (1999) Regulation of p190 Rho-GAP by v-src is linked to cytoskeletal disruption during transformation. J.Cell Sci. 112, 947-956.

Fincham, V. J., James, M., Frame, M. C. & Winder, S. J. (2000) Active ERK/MAP kinase is targeted to newly forming cell-matrix adhesions by integrin engagement and v-Src. EMBO J. 19, 2911-2923.

Guan, J.-L. (1997) Role of focal contact adhesion kinase in integrin signaling. Int.J.Biochem.Cell Biol. 29, 1085-1096.

Isenberg, G. (1996) New concepts for signal perception and transduction by the actin cytoskeleton at cell boundaries. Cell & Develop.Biol. 7, 707-715.

Kaverina, I., Rottner, K. & Small, J. V. (1998) Targeting, capture, and stabilization of microtubules at early focal adhesions.  J.Cell Biol. 142, 181-190.

Kaverina, I., Krylyshkina, O. & Small, J. V. (1999) Microtubule targeting of substrate contacts promotes their relaxation and dissociation. J.Cell Biol. 146, 1033-1043.

Kaverina, I., Krylyshkina, O. & Small, J. V. (2002) Regulation of substrate adhesion dynamics during cell motility.  Int. J. Biochem.Cell Biol. 34, 746-761.

Kirchner, J., Kam, Z., Tzur, G., Bershadsky, A. D. & Geiger, B. (2002) Live-cell monitoring of tyrosine phosphorylation in focal adhesions following microtubule disruption. J Cell Sci. 116, 975-986.

Longley, R. L., Woods, A., Fleetwood, A., Cowling, G. J., Gallagher, J. T. & Couchman, J. R. (1999) Control of morphology, cytoskeleton and migration by syndecan-4. J.Cell Sci. 112, 3421-3431.

Manenti, S., Malecaze, F. & Darbon, J. M. (1997) The major myritoylated PKC substrate (MARCKS) is involved in cell spreading , tyrosine phosphorylation of paxillin and focal contact formation. FEBS letters. 419, 95-98.

Nix, D. A. & Beckerle, M. C. (1997) Nuclear-cytoplasmic shuttling of the focal contact protein, zyxin: A potential mechanism for communication between sites of cell adhesion and the nucleus. J.Cell Biol. 138, 1139-1147.

Oakley, C. & Brunette, D. M. (1993) The sequence of alignment of microtubules, focal contacts and actin filaments in fibroblasts spreading on smooth and grooved titanium substratum. J.Cell Sci. 106, 343-354.

Oda, A., Wada, I., Miura, K., Okawa, K., Kadoya, T., Kato, T., Nishihara, H., Maeda, M., Tanaka, S., Nagashima, K., Nishitani, C., Matsuno, K., Ishino, M., Machesky, L. M., Fujita, H. & Randazzo, P. (2003) CrkL Directs ASAP1 to Peripheral Focal Adhesions. J. Biol. Chem. 278, 6456-6460.

 Oshiro, T., Koyama, S., Sugiyama, S., Kondo, A., Onodera, Y., Asahara, T., Sabe, H. & Kikuchi, A. (2002) Interaction of POB1, a Downstream Molecule of Small G Protein Ral, with PAG2, a Paxillin-binding Protein, Is Involved in Cell Migration. J. Biol. Chem. 277, 38618-38626.

Petit, M. M. R., Meukemans, S. M. P. & Van de Ven, W. J. M. (2003) The focal contact adhesion and nuclear targeting capacity of the LIM-containing lipoma-preferred partner (LPP) protein. J.Biol.Chem. 278, 2157-2168.

Riveline, D., Zamir, E., Balaban, N. Q., Schwarz, U. S., Ishizaki, T., Narumiya, S., Kam, Z., Geiger, B. & Bershadsky, A. D. (2001) Focal contacts as mechanosensors: Externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism. J. Cell Biol. 153, 1175-1185.

Sastry, S. K. & Burridge, K. (2000) Focal adhesions: a nexus for intracellular signaling and cytoskeletal dynamics. Exp.Cell Res. 261, 25-36.

Sugiyama, T., Matsuda, Y. & Mikoshiba, K. (2000) Inositol 1,4,5-trisphosphate receptor associated with focal contact cytoskeletal proteins. FEBS letters.

Yamada, K. & Geiger, B. (1997) Molecular interactions in cell adhesion complexes. Curr.Opin.Cell Biol. 9.

Young, B. A., Taooka, Y., Liu, S., Askins, K. J., Yokosaki, Y., Thomas, S. M. & Sheppard, D. (2001) The cytoplasmic domain of the integrin a9 subunit requires the adaptor protein paxillin to inhibit cell spreading but promotes cell migration in a paxillin-independent manner. Mol. Biol. of the Cell. 12, 3214-3225.

Yujiri, T., Nawata, R., Takahashi, T., Sato, Y., Tanizawa, Y., Kitamura, T. & Oka, Y. (2003) MEK Kinase 1 Interacts with Focal Adhesion Kinase and Regulates Insulin Receptor Substrate-1 Expression. J. Biol. Chem. 278, 3846-3851.


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