Focal adhesions: a personal perspective on a half century of progress

Abstract

Focal adhesions (FAs) are specialized sites within the cell where clustered integrin receptors interact with the extracellular matrix on the outside of cells and with the actin cytoskeleton on the inside. They provide strong adhesion to the matrix and transmit mechanical tension generated within cells across the plasma membrane to the external environment. Additionally, they act as scaffolds for many signaling pathways triggered by integrin engagement or mechanical force exerted on cells. Here I describe my personal perspective on FA research which I have witnessed since the initial discovery and description of FAs as electron dense regions of the ventral plasma nearly half a century ago.

Keywords: FAK; RhoA; adhesion plaques; cell migration; focal adhesions; focal complexes; nascent adhesions; stress fibers.

Figure 1

A REF52 fibroblast plated on a collagen-coated glass coverslip, reveals focal adhesions stained for vinculin (green), F-actin (red), showing stress fibers and the nucleus labeled in blue. Image was kindly provided by David Graham.

Figure 2

Early models of focal adhesion structure. In A, a diagram of a FA is shown that I made in ~1984. It is noteworthy both for how few components are represented and the lack of any transmembrane proteins. By 1996, the time of the model shown in B, many more proteins had been identified and a more complex FA architecture is illustrated. This figure is reproduced from Burridge and Chrzanowska-Wodnicka [40].

Figure 3

A schematic model of focal adhesion molecular architecture based on iPALM analysis. Figure reproduced with permission from Kanchanawong et al. [19].