The integrin adhesome: from genes and proteins to human disease

Abstract

The adhesive interactions of cells with their environment through the integrin family of transmembrane receptors have key roles in regulating multiple aspects of cellular physiology, including cell proliferation, viability, differentiation and migration. Consequently, failure to establish functional cell adhesions, and thus the assembly of associated cytoplasmic scaffolding and signalling networks, can have severe pathological effects. The roles of specific constituents of integrin-mediated adhesions, which are collectively known as the 'integrin adhesome', in diverse pathological states are becoming clear. Indeed, the prominence of mutations in specific adhesome molecules in various human diseases is now appreciated, and experimental as well as in silico approaches provide insights into the molecular mechanisms underlying these pathological conditions.

The FERM protein EPB41L5 regulates actomyosin contractility and focal adhesion formation to maintain the kidney filtration barrier

“…FAs are multiprotein complexes that sense the ECM environment, integrate incoming signals, and mediate required contractile forces for adhesion adjustment (Fig. 1D) (9). To identify podocyte adhesome-associated proteins, we made use of a genetically encoded reporter mouse system (Fig.…”

“…Integrin receptors are linked to an intracellular multiprotein complex, collectively named the integrin adhesome, constituting various adaptor proteins, GTPases, kinases, and phosphatases (9). One common form of integrin-mediated adhesion is focal adhesions (FAs), which have been extensively studied in cultured cells (9). Functionally, FAs support the physical interaction of cells to the ECM, establish connection to the actomyosin Significance Loss of podocyte adhesion is a hallmark of glomerular disease progression.…”

“…On a molecular level, a multitude of adhesion receptors including heterodimeric integrins mediate interaction of cells with the surrounding extracellular matrix (ECM) or the basement membrane (8,9). Integrin receptors are linked to an intracellular multiprotein complex, collectively named the integrin adhesome, constituting various adaptor proteins, GTPases, kinases, and phosphatases (9).…”

“…Integrin receptors are linked to an intracellular multiprotein complex, collectively named the integrin adhesome, constituting various adaptor proteins, GTPases, kinases, and phosphatases (9). One common form of integrin-mediated adhesion is focal adhesions (FAs), which have been extensively studied in cultured cells (9).…”

Loss of mouse cardiomyocyte talin-1 and talin-2 leads to β-1 integrin reduction, costameric instability, and dilated cardiomyopathy

“…It is recognized that this structure is important for organizing and regulating the mechanical and signaling events that occur upon cellular adhesion to ECM (7,8). In addition, it is clear that there are other types of matrix adhesions in addition to the FA, and furthermore, that there can be substantial variation in these structures when studied in 2D cultured cells vs. 3D systems more akin to that found in vivo in tissues/organs such as the heart.…”