The Molecular Architecture of Focal Adhesions

Abstract

This article outlines the present knowledge of the architecture, molecular composition, and dynamics of focal contacts of adhesive animal cells. These structures, developed at the plasma membrane at sites where cells touch their substratum, are essential for cellular attachment in tissue formation during embryogenesis and wound healing. In tissue culture, they are particularly prominent and thus amenable to detailed investigation. Focal contacts consist of a cytoplasmic face, comprising cytoskeletal elements, a transmembrane connecting region, and a extracellular face composed of proteins of the extracellular matrix. The molecular anatomy of the numerous proteins involved, the basis for classifying them as structural or regulatory components, and their in vitro interactions are described. Based on this information, current models on the dynamics of their assembly and of possible regulatory mechanisms involving a variety of signal transduction pathways are discussed.

Involvement of Cdc42 small G protein in cell-cell adhesion, migration and morphology of MDCK cells

“…Several peripheral membrane proteins, including ZO-1, ZO-2, cingulin, the 7H6 antigen, Rab13 small G protein, and symplekin, are localized at tight junction (Citi et al, 1988;Woods and Bryant, 1993;Zhong et al, 1993;Jesaitis and Goodenough, 1994;Zahraoui et al, 1994;Keon et al, 1996). At cell-matrix junction, integrins interact with matrix proteins at the extracellular surface and indirectly interact at the cytoplasmic region with the actin cytoskeleton through many peripheral membrane proteins, including talin, tensin, vinculin, focal adhesion kinase, paxillin, a-actinin, and nexilin (Wilkins et al, 1986;Turner et al, 1990;Schaller et al, 1992;Ohtsuka et al, 1998; for reviews, see Jockusch et al, 1995;Burridge and ChrzanowskaWodnicka, 1996).…”

Intramolecular interactions regulate serine/threonine phosphorylation of vinculin

“…Vinculin is one of the major structural proteins located at the cytoplasmic face of microfilament-dependent cell-cell and cell-matrix adhesions of animal cells [1,2]. The 116 kDa protein consists of a large, roughly globular head domain and a smaller, rod-like tail domain of approx.…”

“…Similarly, cell adhesion is disturbed in cultered fibroblasts microinjected with antibodies against vinculin [8][9][10]. Recent studies have shown that vinculin is a multi-ligand protein that interacts in vitro with other components of cell-contact sites, like talin, a-actinin, F-actin, paxillin and acidic phospholipids (for review see [1]). The binding of most, if not all of these ligands seems to be modulated by a head-tail interaction in the vinculin molecule itself [11][12][13][14][15].…”

Protein kinase C and F‐actin are essential for stimulation of neuronal FAK tyrosine phosphorylation by G‐proteins and amyloid beta protein

“…It now is well recognized that F-actin-dependent signaling plays a central role in regulatory cell biology [2]. Various lines of evidence also indicate a role for actin-associated signaling in synaptic plasticity [18].…”

“…It is coupled to intricate protein-protein interactions associated with filamentous actin and components of focal adhesions [2]. Tyr(P) of FAK increases its own kinase activity and establishes a target sequence that can be bound by SH2 domains of other lattice-forming signal transduction proteins.…”