Caco-2 cells labeled for tight junction molecule cingulin (green), actin (red), vinculin (pink) and DNA (blue).
Epithelial cells growing on a patterned adhesive surface with the shape of the Weizmann Institute tree.
Desmosomes in mouse tongue epithelium (by transmission electron microscope).
Porcine aortic endothelial cell, double-labeled for actin (green) and phospho-tyrosine (red).
“Molecular composition map” of focal adhesions and stress fibers.
Myeloma cancer cell responding to shear flow (by scanning electron microscope).
Adhesion diversity and the integrin adhesome network
Upon binding of integrins to the extracellular matrix, a large number of proteins are recruited to these nascent adhesions that ultimately connect the extracellular matrix to the actin cytoskeleton. The components comprising these adhesion sites are collectively referred to as the “integrin adhesome” (Figure 1) (see Zaidel-Bar et al., (2007).
Figure 1
Adhesion Diversity and the Integrin Adhesome Network. This network is divided here into structural (center) and regulatory/signaling (left and right) sub-networks. The structural part consists of actin, integrins (ITGA, ITGB) and other adhesion receptors (light brown ellipses), cytoskeletal proteins (cyan ellipses), actin modulators (light green), and multidomain adaptor proteins (red). The regulatory/signaling part includes small GTPase proteins and their activators and inhibitors (blue hexagons, rectangles, and ellipses, respectively), tyrosine kinases and phosphatases (orange rectangles and ellipses), serine/threonine kinases and phosphatases (yellow rectangles and ellipses), phospholipids (and their hydrolysis products), phosphatidylinositol kinases, phosphatidylinositol phosphatases and phospholipases (pink hexagons, rectangles, ellipses, and diamonds), chaperones and mediators of protein degradation (black and gray), and regulators of transcription and translation (mint green rectangles). Integrin adhesome data are largely based on Zaidel-Bar R and Geiger B (2010) The switchable integrin adhesome. Journal of Cell Science 123: 1385–1388, and http://www.adhesome.org.
For an updated list of adhesome components, see Winograd-Katz et al., (2014). Integrin adhesions are a family of diverse matrix contact sites (e.g. focal complexes, focal adhesions, fibrillar adhesions, podosomes, invadopodia), with multiple ubiquitous proteins as well as proteins that are specifically associated with only some of the “sub-families”. We refer to specific molecules as “adhesome components”. Some of the adhesome molecules are permanent residents on integrin adhesions (intrinsic molecules), whereas others are transiently associated with the adhesion sites, and affect their properties (associated molecules). Some of the adhesome constituents, mainly those that are involved in the mechanical linking of integrin to the cytoskeleton, are considered as “scaffolding components” while signaling molecules that interact with the adhesion (kinases and phosphatases, as well as different Rho family GTPases and their positive [GEFs] or negative [GAPs] regulators) are believed to have a regulatory function (Figure 2).
Figure 2
Adhesion-mediated Signaling. Interactions between functional families of adhesome components. Each protein in the adhesome was categorized into one of 19 groups according to its known biological activity. The families are shown in unique combinations of colour and shape, indicating the number of family members followed by the average number of their interactions. In addition, the dominating interactions between families (red arrows, activating interactions; blue arrows, inhibiting interactions; black lines, binding interactions) are shown.
Recent studies have addressed the diverse functions of the adhesome network, including the modulation of its connectivity by the signaling molecule, and its involvement in disease (Figure 3).
Figure 3
Adhesome genes grouped by their functional categories. Intrinsic genes are in normal text while associated ones are in italics. Genes names are colored based on the kind of disease they produce when mutated (OMIM list). The color key is described on the top of the cell.
In addition, it is noteworthy that different regions within focal adhesions as well as different forms of integrin adhesions display distinct molecular composition.
Further Reading
