Focal Contacts

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
a-actinin
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;
Talin
Tes		Coutts et al, 2003;
Vinculin
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.

References:-

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.