FAK Structure and Regulation by Membrane Interactions and Force in Focal Adhesions

Martínez, Paula Tapial; Navajas, Pilar López; Lietha, Daniel

doi:10.3390/biom10020179

Cited by 150 publications

(105 citation statements)

References 95 publications

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“…Between the cytoplasmic domain of the β subunit and cytoskeletal protein, actin, there are adaptor proteins including talin, vinculin, and paxillin. Focal adhesion kinase (Fak) and Src kinase family members, which are tyrosine kinases, are also located therein; and these molecules are involved in the formation of focal adhesions [38] . On the other hand, the actin cytoskeleton exists in 2 forms, monomeric globular actin (G-actin) and filamentous actin (F-actin); and it regulates cell shape by the conversion between G- and F-actin [29] .…”

Section: Mechanoreceptors That Sense Mechanical Stressmentioning

confidence: 99%

Roles of CCN2 as a mechano-sensing regulator of chondrocyte differentiation

Nishida

Kubota

2020

Japanese Dental Science Review

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Cellular communication network factor 2 (CCN2) is a cysteine-rich secreted matricellular protein that regulates various cellular functions including cell differentiation. CCN2 is highly expressed under several types of mechanical stress, such as stretch, compression, and shear stress, in mesenchymal cells including chondrocytes, osteoblasts, and fibroblasts. In particular, CCN2 not only promotes cell proliferation and differentiation of various cells but also regulates the stability of mRNA of TRPV4, a mechanosensitive ion channel in chondrocytes. Of note, CCN2 behaves like a biomarker to sense suitable mechanical stress, because CCN2 expression is down-regulated when chondrocytes are subjected to excessive mechanical stress. These findings suggest that CCN2 is a mechano-sensing regulator. CCN2 expression is regulated by the activation of various mechano-sensing signaling pathways, e.g., mechanosensitive ion channels, integrin-focal adhesion-actin dynamics, Rho GTPase family members, Hippo-YAP signaling, and G protein-coupled receptors. This review summarizes the characterization of mechanoreceptors involved in CCN2 gene regulation and discusses the role of CCN2 as a mechano-sensing regulator of mesenchymal cell differentiation, with particular focus on chondrocytes.

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Section: Mechanoreceptors That Sense Mechanical Stressmentioning

confidence: 99%

Roles of CCN2 as a mechano-sensing regulator of chondrocyte differentiation

Nishida

Kubota

2020

Japanese Dental Science Review

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“…Polarized cell migration requires activation of integrin-mediated cell adhesion, which is translated to changes in the phosphorylation status of mechanically sensitive proteins ( Tapial Martinez et al. , 2020 ).…”

Section: Resultsmentioning

confidence: 99%

“…Linking the ECM to the intracellular cytoskeletal network are dynamic, integrin-based protein complexes referred to as focal adhesions (FAs). FA dynamics are essential for directional cell migration, as they are formed at sites of cell adhesion to the ECM and mediate mechanotransduction and integrin signaling ( Tapial Martinez et al. , 2020 ).…”

Section: Introductionmentioning

confidence: 99%

An IFT20 mechanotrafficking axis is required for integrin recycling, focal adhesion dynamics, and polarized cell migration

Begum

Ezratty

2020

MBoC

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Directional cell migration drives embryonic development, cancer metastasis, tissue repair and regeneration. Here, we examine the role of Intraflagellar Transport 20 (Ift20) during polarized migration of epidermal cells. IFT20 is implicated in regulating cell migration independently of the primary cilium, but how IFT proteins integrate with the cell migration machinery is poorly understood. We show that genetic ablation of IFT20 in vitro slows keratinocyte migration during wound healing. We find that this phenotype is independent of the primary cilium and instead can be attributed to alterations in integrin mediated mechano-transduction and focal adhesion (FA) dynamics. Loss of Ift20 resulted in smaller and less numerous FAs, and reduced levels of activated FAK. Studies of FA dynamics during microtubule-induced FA turnover demonstrated that Ift20 loss specifically impaired the reformation, but not the disassembly, of FAs. In the absence of Ift20 function, β1 integrins endocytosed during FA disassembly are not transferred out of Rab5 (+) endosomes. This defective transit from the early endosome disrupts eventual recycling of β1-integrins back to the cell surface, resulting in defective FA reformation. In vivo, conditional ablation of Ift20 in hair follicle stem cells (HF-SCs) similarly impairs their ability to invade and migrate during epidermal wound healing. Using explant studies, lineage-tracing and clonal analysis we demonstrate that Ift20 is required for HF-SC migration and their contribution to epidermal regeneration. This work identifies a new Ift20 mechano-trafficking mechanism required for polarized cell migration and stem cell-driven tissue repair.

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“…Ezrin forms a functional triagle, including protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), and Git1. Protein tyrosine kinase 2 (PTK2) is a non-receptor tyrosine-protein kinase [63]; it directly interacts with Ezrin in connections of major cytoskeleton structures to the plasma membrane [62]. FAK (PTK2) can directly interact with Fyn, a member of the Src family of protein tyrosine kinases (SFKs) in lipid rafts [64].…”

Section: Discussionmentioning

confidence: 99%

A Neuroprotective Dose of Isatin Causes Multilevel Changes Involving the Brain Proteome: Prospects for Further Research

Медведев

Kopylov

Buneeva

et al. 2020

IJMS

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Isatin (indole-2,3-dione) is an endogenous regulator, exhibiting a wide range of biological and pharmacological activities. At doses of 100 mg/kg and above, isatin is neuroprotective in different experimental models of neurodegeneration. Good evidence exists that its effects are realized via interaction with numerous isatin-binding proteins identified in the brain and peripheral tissues studied. In this study, we investigated the effect of a single dose administration of isatin to mice (100 mg/kg, 24 h) on differentially expressed proteins and a profile of the isatin-binding proteins in brain hemispheres. Isatin administration to mice caused downregulation of 31 proteins. However, these changes cannot be attributed to altered expression of corresponding genes. Although at this time point isatin influenced the expression of more than 850 genes in brain hemispheres (including 433 upregulated and 418 downregulated genes), none of them could account for the changes in the differentially expressed proteins. Comparative proteomic analysis of brain isatin-binding proteins of control and isatin-treated mice revealed representative groups of proteins sensitive to isatin administration. Control-specific proteins (n = 55) represent specific targets that interact directly with isatin. Appearance of brain isatin-binding proteins specific to isatin-treated mice (n = 94) may be attributed to the formation of new clusters of protein–protein interactions and/or novel binding sites induced by a high concentration of this regulator (ligand-induced binding sites). Thus, isatin administration produces multiple effects in the brain, which include changes in gene expression and also profiles of isatin-binding proteins and their interactomes. Further studies are needed for deeper insight into the mechanisms of the multilevel changes in the brain proteome induced by isatin. In the context of the neuroprotective action, these changes may be aimed at interruption of pathological links that begin to form after initiation of pathological processes.

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FAK Structure and Regulation by Membrane Interactions and Force in Focal Adhesions

Cited by 150 publications

References 95 publications

Roles of CCN2 as a mechano-sensing regulator of chondrocyte differentiation

Roles of CCN2 as a mechano-sensing regulator of chondrocyte differentiation

An IFT20 mechanotrafficking axis is required for integrin recycling, focal adhesion dynamics, and polarized cell migration

A Neuroprotective Dose of Isatin Causes Multilevel Changes Involving the Brain Proteome: Prospects for Further Research

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