Dynamic Regulation of the Structure and Functions of Integrin Adhesions

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Developmental Cell (Impact Factor: 9.71). 03/2013; 24(5):447-58. DOI: 10.1016/j.devcel.2013.02.012
Source: PubMed


Integrin-mediated cell adhesions to the extracellular matrix (ECM) contribute to tissue morphogenesis and coherence and provide cells with vital environmental cues. These apparently static structures display remarkable plasticity and dynamic properties: they exist in multiple, interconvertible forms that are constantly remodeled in response to changes in ECM properties, cytoskeletal organization, cell migration, and signaling processes. Thus, integrin-mediated environmental sensing enables cells to adapt to chemical and physical properties of the surrounding matrix by modulating their proliferation, differentiation, and survival. This intriguing interplay between the apparently robust structure of matrix adhesions and their highly dynamic properties is the focus of this article.

Download full-text


Available from: Haguy Wolfenson, Apr 25, 2014
  • Source
    • "Cell- ECM attachment is mediated by a connection termed the adhesion nexus that consists of clustered transmembrane adhesion proteins, typically integrins, and associated adaptor and signalling proteins (Wehrel-Haller, 2012). These complexes couple ECM fibres to the intracellular cytoskeleton as well as acting as scaffolding and signalling hubs to mediate a diverse array of cellular processes such as migration and proliferation (Wolfenson et al. 2013). Biochemical analysis of adhesion complex composition has primarily been performed in a candidate based manner and has focused on the immunoprecipitation of individual adhesion components. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The integration of cells with their extracellular environment is facilitated by cell surface adhesion receptors, such as integrins, which play important roles in both normal development and the onset of pathologies. Engagement of integrins with their ligands in the extracellular matrix, or counter-receptors on other cells, initiates the intracellular assembly of a wide variety of proteins into adhesion complexes such as focal contacts, focal adhesions, and fibrillar adhesions. The proteins recruited to these complexes mediate bidirectional signaling across the plasma membrane, and, as such, help to coordinate and/or modulate the multitude of physical and chemical signals to which the cell is subjected. The protocols in this unit describe two approaches for the isolation or enrichment of proteins contained within integrin-associated adhesion complexes, together with their local plasma membrane/cytosolic environments, from cells in culture. In the first protocol, integrin-associated adhesion structures are affinity isolated using microbeads coated with extracellular ligands or antibodies. The second protocol describes the isolation of ventral membrane preparations that are enriched for adhesion complex structures. The protocols permit the determination of adhesion complex components via subsequent downstream analysis by western blotting or mass spectrometry. © 2015 by John Wiley & Sons, Inc. Copyright © 2015 John Wiley & Sons, Inc.
    Full-text · Article · Mar 2015 · Current protocols in cell biology / editorial board, Juan S. Bonifacino ... [et al.]
  • Source
    • "Primary mechanosensors are located at the plasma membrane and can directly mediate the conversion of mechanical signals into biochemical signals (Fig. 1). Such sensors comprise integrins mediating cell attachment to the ECM, cell–cell adhesion molecules such as platelet endothelial cell adhesion molecule-1 (PECAM1), vascular endothelial growth factor receptor 2 (VEGFR2), mechanosensory complexes on endothelial cells such as VE cadherin (Fig. 2), and stretchactivatable ion channels (Tzima et al. 2005; Davies 2009; Wolfenson et al. 2013; Janostiak et al. 2014; Leckband and de Rooij 2014; Yao et al. 2014 "
    [Show abstract] [Hide abstract]
    ABSTRACT: The intermediate filament proteins, A- and B-type lamins, form the nuclear lamina scaffold adjacent to the inner nuclear membrane. B-type lamins confer elasticity, while A-type lamins lend viscosity and stiffness to nuclei. Lamins also contribute to chromatin regulation and various signaling pathways affecting gene expression. The mechanical roles of lamins and their functions in gene regulation are often viewed as independent activities, but recent findings suggest a highly cross-linked and interdependent regulation of these different functions, particularly in mechanosignaling. In this newly emerging concept, lamins act as a "mechanostat" that senses forces from outside and responds to tension by reinforcing the cytoskeleton and the extracellular matrix. A-type lamins, emerin, and the linker of the nucleoskeleton and cytoskeleton (LINC) complex directly transmit forces from the extracellular matrix into the nucleus. These mechanical forces lead to changes in the molecular structure, modification, and assembly state of A-type lamins. This in turn activates a tension-induced "inside-out signaling" through which the nucleus feeds back to the cytoskeleton and the extracellular matrix to balance outside and inside forces. These functions regulate differentiation and may be impaired in lamin-linked diseases, leading to cellular phenotypes, particularly in mechanical load-bearing tissues. © 2015 Osmanagic-Myers et al.; Published by Cold Spring Harbor Laboratory Press.
    Full-text · Article · Feb 2015 · Genes & Development
  • Source
    • "Focal contacts are nascent cell adhesions that form behind the cell leading edge; these are transformed into longer structures (focal adhesions) that provide firm adhesion via actomyosin stress fibers; focal adhesions also develop into centrally located fibrillar adhesions that mediate strong adhesion (Wolfenson et al., 2013). The capacity of p85b to enlarge the number of centrally localized larger cell adhesions concurs with p85b enhancement of cell adhesion, as centrally localized adhesions mediate firm adhesion (Wolfenson et al., 2013). p85b involvement in cell adhesion maturation is also suggested by the TIRFM analysis, in this assay p85b depletion reduced paxillin intensity and area and impaired the movement of cell adhesions to the cell center; adhesions were significantly less stable (Fig. 6). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The acquisition of invasiveness is characteristic of tumor progression. Numerous genetic changes are associated with metastasis, but the mechanism by which a cell becomes invasive remains unclear. Expression of p85β, a regulatory subunit of phosphoinositide-3-kinase, markedly increases in advanced carcinoma, but its mode of action is unknown. We postulated that p85β might facilitate cell invasion. We show that p85β localized at cell adhesions in complex with focal adhesion kinase and enhanced stability and maturation of cell adhesions. In addition, p85β induced development at cell adhesions of an F-actin core that extended several microns into the cell z-axis resembling the skeleton of invadopodia. p85β lead to F-actin polymerization at cell adhesions by recruiting active Cdc42/Rac at these structures. In accordance with p85β function in invadopodium-like formation, p85β levels increased in metastatic melanoma and p85β depletion reduced invadopodium formation and invasion. These results show that p85β enhances invasion by inducing cell adhesion development into invadopodia-like structures explaining the metastatic potential of tumors with increased p85β levels.
    Full-text · Article · Sep 2014 · Biology Open
Show more