Definition of a consensus integrin adhesome and its dynamics during adhesion complex assembly and disassembly

Abstract

Integrin receptor activation initiates the formation of integrin adhesion complexes (IACs) at the cell membrane that transduce adhesion-dependent signals to control a multitude of cellular functions. Proteomic analyses of isolated IACs have revealed an unanticipated molecular complexity; however, a global view of the consensus composition and dynamics of IACs is currently lacking. Here, we have integrated several IAC proteomes and generated a 2,412-protein integrin adhesome. Analysis of this dataset reveals the functional diversity of proteins in IACs and establishes a consensus adhesome of 60 proteins. The consensus adhesome likely represents a core cell adhesion machinery, centred around four axes comprising ILK-PINCH-kindlin, FAK-paxillin, talin-vinculin and α-actinin-zyxin-VASP, and includes underappreciated IAC components such as Rsu-1 and caldesmon. Proteomic quantification of IAC assembly and disassembly detailed the compositional dynamics of the core cell adhesion machinery. The definition of this consensus view of integrin adhesome components provides a resource for the research community.

LAR protein tyrosine phosphatase regulates focal adhesions through CDK1

“…A cluster of 38 proteins containing predicted CDK1 phosphorylation motifs were identified with significantly reduced phosphorylation in LARΔP cells. Of these, 19 (50%) formed part of the recently characterised meta-adhesome (Horton et al, 2015) (Fig. 4A).…”

“…Proteins localizing to focal adhesions include structural proteins that link integrins to the actin cytoskeleton as well as many other proteins involved in signal transduction. These include the well-documented regulators of focal adhesions, Src and focal adhesion kinase (FAK, also known as PTK2) but also other kinases including members of the cyclin-dependent kinase (CDK) family (Horton et al, 2015;Robertson et al, 2015;Zaidel-Bar et al, 2007). The extracellular domain of LAR is known to interact with components of the extracellular matrix including the lamininnidogen complex and syndecan (Johnson et al, 2006;O'Grady et al, 1998), and imaging and proteomic studies have established that LAR is a component of focal adhesions and can regulate the actin cytoskeleton (Serra-Pages et al, 1995;Zaidel-Bar et al, 2007).…”

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

“…1E) (17). We further refined our initial list by integrating recently published experimental data (18) and ended up with a list of 182 potential podocyte-enriched FA proteins (Dataset S1). EPB41L5 appeared as the top enriched protein in our candidate approach after applying different filtering steps for FA-associated protein domains (Dataset S1).…”

A dual phenotype of MDA-MB-468 cancer cells reveals mutual regulation of tensin3 and adhesion plasticity

“…It is evident that the precise molecular composition of these integrin-based adhesion complexes is critical for their function. Depending on the cell type, the so-called 'integrin adhesome' can vary a lot and several hundreds of proteins contribute to the adhesome, as revealed by proteomic analyses (Humphries and Reynolds, 2009;Schiller et al, 2011;Horton et al, 2015). On the basis of function, composition and appearance cell−matrix adhesions can be classified (Sun et al, 2016).…”