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Alexander Bershadsky

Publications and source records attributed to Alexander Bershadsky.

7 recordsLinked to original sources
PubMed2006

Adhesion-mediated mechanosensitivity: a time to experiment, and a time to theorize.

Adhesion-mediated signaling provides cells with information about multiple parameters of their microenvironment, including mechanical characteristics. Often, such signaling is based on a unique feature of adhesion structures: their ability to grow and strengthen when force is applied to them, either from within the cell or from the outside. Such adhesion reinforcement is characteristic of integrin-mediated cell-matrix adhesions, but may also operate in other types of adhesion structures. Though the amount of knowledge about adhesion-mediated signaling is growing rapidly, the mechanisms underlying force-dependent regulation of junction assembly are largely unknown. Experiments have been carried out that have started to uncover the major signaling pathways involved in the response of adhesion sites to force. Theoretical models have also been used to address the physical mechanisms underlying adhesion-mediated mechanosensing.

Animals↗
PubMed2006

Molecular mapping of tyrosine-phosphorylated proteins in focal adhesions using fluorescence resonance energy transfer.

Microscopy-based fluorescence resonance energy transfer (FRET) provides an opportunity to monitor molecular processes in the natural environment in live cells. Here we studied molecular interactions and tyrosine phosphorylation of paxillin, Crk-associated substrate (CAS), and focal adhesion kinase (FAK) in focal adhesions. For that purpose, these focal adhesion phosphoproteins, fused to cyan or yellow fluorescent proteins (CFP or YFP) were expressed in cultured fibroblasts. To assess the dynamics of tyrosine phosphorylation we used YFP- or CFP-tagged SH2 domain of pp60(src) (dSH2), which specifically binds to phosphotyrosine residues. FRET measurements, combined with immunolabeling with phosphospecific antibodies revealed that FAK, CAS and paxillin are tyrosine phosphorylated in early matrix adhesions and that FAK is in FRET proximity to CAS and paxillin in focal complexes and focal adhesions. Data suggest that paxillin incorporation into nascent focal complexes precedes its tyrosine phosphorylation, which then gradually increases. In cells treated with Rho-kinase inhibitors or expressing constitutively active Rac, focal complexes showed similar levels of paxillin tyrosine phosphorylation as seen in mature focal adhesions. Dynamic FRET-based examination indicated that paxillin phosphorylation occurs in specific areas (hotspots) within focal adhesions, whereas FAK phosphorylation is broadly distributed.

Animals↗
PubMed2004

Magic touch: how does cell-cell adhesion trigger actin assembly?

The formation of cadherin-mediated cell-cell junctions is accompanied by a profound remodeling of the actin cytoskeleton. The Arp2/3 complex and its activator cortactin drive the assembly of branching actin-filament arrays, and formin-1 promotes the nucleation of non-branching actin filaments. Recruitment of these actin nucleators to nascent adhesions, formation of the links between them and the cytoplasmic cadherin domain, and triggering of their actin-polymerizing functions are vital steps in the development of cell-cell junctions. In this article, I discuss recent results showing that proteins involved in the regulation of actin polymerization have crucial roles in the development and maintenance of the cadherin junctions.

Actins↗
PubMed2003

Lamellipodium extension and cadherin adhesion: two cell responses to cadherin activation relying on distinct signalling pathways.

Cell adhesion molecules of the cadherin family contribute to the regulation of cell shape and fate by mediating strong intercellular adhesion through Ca2+-dependent interaction of their ectodomain and association of their cytoplasmic tail to actin. However, the mechanisms co-ordinating cadherinmediated adhesion with the reorganization of the actin cytoskeleton remain elusive. Here, the formation of de novo contacts was dissected by spreading cells on a highly active N-cadherin homophilic ligand. Cells responded to N-cadherin activation by extending lamellipodium and organizing cadherin-catenin complexes and actin filaments in cadherin adhesions. Lamellipodium protrusion, associated with actin polymerization at the leading edge sustained the extension of cadherin contacts through a phosphoinositide 3-kinase (PI 3-kinase)-Rac1 pathway. Cadherin adhesions were formed by PI 3-kinase-independent, Rac1-dependent co-recruitment of adhesion complexes and actin filaments. The expression and localization of p120 at the plasma membrane, associated with an increase in membrane-associated Rac1 was required for both cell responses, consistent with a major role of p120 in signalling pathways initiated by cadherin activation and contributing to Rac1-dependent contact extension and maturation. These results provide additional information on the mechanisms by which cadherin coordinates adhesion with dynamic changes in the cytoskeleton to control cell shape and intercellular junction organization.

Animals↗
PubMed2002

Exploring the neighborhood: adhesion-coupled cell mechanosensors.

Here we discuss recent studies addressing adhesion-coupled mechanosensory processes and consider their molecular nature. Are cells using stretch-activated ion channels to explore the extracellular environment surrounding them, or do they use for that purpose the submembrane protein network that interconnects integrin receptors with the actin cytoskeleton?

Animals↗
PubMed2002

How do microtubules guide migrating cells?

Microtubules have long been implicated in the polarization of migrating cells, but how they carry out this role is unclear. Here, we propose that microtubules determine cell polarity by modulating the pattern of adhesions that a cell develops with the underlying matrix, through focal inhibitions of contractility.

Actins↗