Cell adhesion to the extracellular matrix is essential for cellular processes, such as migration and invasion. In response to cues from the microenvironment, integrin-mediated adhesions alter cellular behaviour through cytoskeletal rearrangements. The tight association of the actin cytoskeleton with adhesive structures has been extensively studied, whereas the microtubule network in this context has gathered far less attention. In recent years, however, microtubules have emerged as key regulators of cell adhesion and migration through their participation in adhesion turnover and cellular signalling. In this Review, we focus on the interactions between microtubules and integrin-mediated adhesions, in particular, focal adhesions and podosomes. Starting with the association of microtubules with these adhesive structures, we describe the classical role of microtubules in vesicular trafficking, which is involved in the turnover of cell adhesions, before discussing how microtubules can also influence the actin-focal adhesion interplay through RhoGTPase signalling, thereby orchestrating a very crucial crosstalk between the cytoskeletal networks and adhesions.
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http://dx.doi.org/10.1242/jcs.232843 | DOI Listing |
J Cell Physiol
January 2025
Department of Biosciences & Bioengineering, IIT Bombay, Mumbai, India.
In addition to proteins such as collagen (Col) and fibronectin, the extracellular matrix (ECM) is enriched with bulky proteoglycan molecules such as hyaluronic acid (HA). However, how ECM proteins and proteoglycans collectively regulate cellular processes has not been adequately explored. Here, we address this question by studying cytoskeletal and focal adhesion organization and dynamics on cells cultured on polyacrylamide hydrogels functionalized with Col, HA and a combination of Col and HA (Col/HA).
View Article and Find Full Text PDFFront Cell Dev Biol
January 2025
Mathematical Institute, Faculty of Science, Leiden University, Leiden, Netherlands.
Many mammalian cells, including endothelial cells and fibroblasts, align and elongate along the orientation of extracellular matrix (ECM) fibers in a gel when cultured . During cell elongation, clusters of focal adhesions (FAs) form near the poles of the elongating cells. FAs are mechanosensitive clusters of adhesions that grow under mechanical tension exerted by the cells' pulling on the ECM and shrink when the tension is released.
View Article and Find Full Text PDFACS Chem Biol
January 2025
Department of Pediatric Dentistry, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, and Shandong Key Laboratory of Oral Tissue Regeneration, Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration, Shandong Provincial Clinical Research Center for Oral Diseases, Jinan 250012, China.
Chronic kidney fibrosis poses a significant global health challenge with effective therapeutic strategies remaining elusive. While cell-extracellular matrix (ECM) interactions are known to drive fibrosis progression, the specific role of focal adhesions (FAs) in kidney fibrosis is not fully understood. In this study, we investigated the role of FAs in kidney tubular epithelial cell fibrosis by employing precise nanogold patterning to modulate integrin distribution.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Emory University, Chemistry, 1515 Dickey Dr., 30322, Atlanta, UNITED STATES OF AMERICA.
Genetically encoded tension sensors (GETSs) allow for quantifying forces experienced by intracellular proteins involved in mechanotransduction. The vast majority of GETSs are comprised of a FRET pair flanking an elastic "spring-like" domain that gradually extends in response to force. Because of ensemble averaging, the FRET signal generated by such analog sensors conceals forces that deviate from the average, and hence it is unknown if a subset of proteins experience greater magnitudes of force.
View Article and Find Full Text PDFPaxillin (PXN) and focal adhesion kinase (FAK) are two major components of the focal adhesion complex, a multiprotein structure linking the intracellular cytoskeleton to the cell exterior. PXN interacts directly with the C-terminal targeting domain of FAK (FAT) via its intrinsically disordered N-terminal domain. This interaction is necessary and sufficient for localizing FAK to focal adhesions.
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