The integrin adhesome network at a glance

Horton, Edward R.; Humphries, Jonathan D.; James, Jennifer E.; Jones, Max; Askari, Janet A.; Humphries, Martin J.

doi:10.1242/jcs.192054

Cited by 199 publications

(150 citation statements)

References 52 publications

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“…This identified a network of > 240 proteins 1, 2, and additional adhesome proteins are constantly being discovered, many of which are cytoplasmic components that couple adhesions to numerous signalling cascades. These enable diverse intracellular responses, a process often referred to as ‘outside‐in’ signalling.…”

Section: Integrin Adhesions: Linking the Cell To The Extracellular Mamentioning

confidence: 99%

The tale of two talins – two isoforms to fine‐tune integrin signalling

Gough

Goult

2018

FEBS Letters

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Talins are cytoplasmic adapter proteins essential for integrin‐mediated cell adhesion to the extracellular matrix. Talins control the activation state of integrins, link integrins to cytoskeletal actin, recruit numerous signalling molecules that mediate integrin signalling and coordinate recruitment of microtubules to adhesion sites via interaction with KANK (kidney ankyrin repeat‐containing) proteins. Vertebrates have two talin genes, TLN1 and TLN2. Although talin1 and talin2 share 76% protein sequence identity (88% similarity), they are not functionally redundant, and the differences between the two isoforms are not fully understood. In this Review, we focus on the similarities and differences between the two talins in terms of structure, biochemistry and function, which hint at subtle differences in fine‐tuning adhesion signalling.

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Section: Integrin Adhesions: Linking the Cell To The Extracellular Mamentioning

confidence: 99%

The tale of two talins – two isoforms to fine‐tune integrin signalling

Gough

Goult

2018

FEBS Letters

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“…Integrins consist of 24 heterodimeric family members comprising α and β chains, which facilitate the anchoring of cells to the extracellular matrix in healthy tissues [44]. It is now well established that H. pylori and its cag T4SS exploit integrin α 5 β 1 as a receptor for CagA translocation [24,26,45,46].…”

Section: Type IV Secretion-dependent Delivery Of Caga Via Integrin-β1mentioning

confidence: 99%

Type IV Secretion and Signal Transduction of Helicobacter pylori CagA through Interactions with Host Cell Receptors

Backert

Tegtmeyer

2017

Toxins

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Helicobacter pylori is a highly successful human bacterium, which is exceptionally equipped to persistently inhabit the human stomach. Colonization by this pathogen is associated with gastric disorders ranging from chronic gastritis and peptic ulcers to cancer. Highly virulent H. pylori strains express the well-established adhesins BabA/B, SabA, AlpA/B, OipA, and HopQ, and a type IV secretion system (T4SS) encoded by the cag pathogenicity island (PAI). The adhesins ascertain intimate bacterial contact to gastric epithelial cells, while the T4SS represents an extracellular pilus-like structure for the translocation of the effector protein CagA. Numerous T4SS components including CagI, CagL, CagY, and CagA have been shown to target the integrin-β1 receptor followed by translocation of CagA across the host cell membrane. The interaction of CagA with membrane-anchored phosphatidylserine and CagA-containing outer membrane vesicles may also play a role in the delivery process. Translocated CagA undergoes tyrosine phosphorylation in C-terminal EPIYA-repeat motifs by oncogenic Src and Abl kinases. CagA then interacts with an array of host signaling proteins followed by their activation or inactivation in phosphorylation-dependent and phosphorylation-independent fashions. We now count about 25 host cell binding partners of intracellular CagA, which represent the highest quantity of all currently known virulence-associated effector proteins in the microbial world. Here we review the research progress in characterizing interactions of CagA with multiple host cell receptors in the gastric epithelium, including integrin-β1, EGFR, c-Met, CD44, E-cadherin, and gp130. The contribution of these interactions to H. pylori colonization, signal transduction, and gastric pathogenesis is discussed.

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“…The overall group of proteins involved in integrin adhesion is termed the integrin adhesome (Zaidel-Bar et al, 2007;Horton et al, 2016), and a subset assembles into integrin adhesion complexes (IACs) that link the ECM to the cytoskeleton. IACs are generally characterised by a discrete structure, as visualised by microscopy, where intracellular integrin-associated proteins (IAPs) become highly concentrated.…”

Section: Introductionmentioning

confidence: 99%

Talin – the master of integrin adhesions

Klapholz

Brown

2017

Journal of Cell Science

263

222

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Talin has emerged as the key cytoplasmic protein that mediates integrin adhesion to the extracellular matrix. In this Review, we draw on experiments performed in mammalian cells in culture and Drosophila to present evidence that talin is the most important component of integrin adhesion complexes. We describe how the properties of this adaptor protein enable it to orchestrate integrin adhesions. Talin forms the core of integrin adhesion complexes by linking integrins directly to actin, increasing the affinity of integrin for ligands (integrin activation) and recruiting numerous proteins. It regulates the strength of integrin adhesion, senses matrix rigidity, increases focal adhesion size in response to force and serves as a platform for the building of the adhesion structure. Finally, the mechano-sensitive structure of talin provides a paradigm for how proteins transduce mechanical signals to chemical signals.

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The integrin adhesome network at a glance

Cited by 199 publications

References 52 publications

The tale of two talins – two isoforms to fine‐tune integrin signalling

The tale of two talins – two isoforms to fine‐tune integrin signalling

Type IV Secretion and Signal Transduction of Helicobacter pylori CagA through Interactions with Host Cell Receptors

Talin – the master of integrin adhesions

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