Regulation of integrin-mediated adhesions

Abstract

Integrins are heterodimeric transmembrane adhesion receptors that couple the actin cytoskeleton to the extracellular environment and bidirectionally relay signals across the cell membrane. These processes are critical for cell attachment, migration, differentiation, and survival, and therefore play essential roles in metazoan development, physiology, and pathology. Integrin-mediated adhesions are regulated by diverse factors, including the conformation-specific affinities of integrin receptors for their extracellular ligands, the clustering of integrins and their intracellular binding partners into discrete adhesive structures, mechanical forces exerted on the adhesion, and the intracellular trafficking of integrins themselves. Recent advances shed light onto how the interaction of specific intracellular proteins with the short cytoplasmic tails of integrins controls each of these activities.

Toxoplasma gondii disrupts β1 integrin signaling and focal adhesion formation during monocyte hypermotility

“…The conformational activation of integrins allows for high-affinity interactions with extracellular ligand to mediate cell crawling and arrest (35). We investigated the effect of T. gondii infection on the ability of activated β1 integrins to cluster, the initial step in focal adhesion formation.…”

Collagen Type I as a Ligand for Receptor-Mediated Signaling

“…Integrins play critical roles in signaling, migration and survival of different cells (recently reviewed in depth by Barczyk et al [5] and Iwamoto and Calderwood [6]). The signaling by these receptors is considered bi-directional, involving outside-in and inside-out signaling [5].…”

“…The signaling by these receptors is considered bi-directional, involving outside-in and inside-out signaling [5]. Integrins function as heterodimers, which in humans include one of 18 distinct α subunits and one of eight distinct β subunits, and are type I transmembrane glycoproteins with large extracellular and short cytoplasmic domains [6]. Four different integrin heterodimers (α 1 β 1 , α 2 β 1 , α 10 β 1 , and α 11 β 1 ) have been demonstrated to bind collagen.…”

Nuclear Localization of Integrin Cytoplasmic Domain-associated Protein-1 (ICAP1) Influences β1 Integrin Activation and Recruits Krev/Interaction Trapped-1 (KRIT1) to the Nucleus

“…Integrin signaling is mediated via interactions between their short cytoplasmic tails and cytoplasmic signaling and scaffolding proteins (2,3). In addition, binding of proteins to the integrin ␤ tails can induce conformational changes in the integrin extracellular domains that alter integrin affinity for extracellular ligands (4). This "inside-out" signaling mechanism alters the integrin activation state and is a key regulator of cell adhesion, cell spreading, cytoskeletal rearrangement, and adhesion signaling.…”