Article

A Role for the Juxtamembrane Cytoplasm in the Molecular Dynamics of Focal Adhesions

Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
PLoS ONE (Impact Factor: 3.53). 02/2009; 4(1):e4304. DOI: 10.1371/journal.pone.0004304
Source: PubMed

ABSTRACT Focal adhesions (FAs) are specialized membrane-associated multi-protein complexes that link the cell to the extracellular matrix and play crucial roles in cell-matrix sensing. Considerable information is available on the complex molecular composition of these sites, yet the regulation of FA dynamics is largely unknown. Based on a combination of FRAP studies in live cells, with in silico simulations and mathematical modeling, we show that the FA plaque proteins paxillin and vinculin exist in four dynamic states: an immobile FA-bound fraction, an FA-associated fraction undergoing exchange, a juxtamembrane fraction experiencing attenuated diffusion, and a fast-diffusing cytoplasmic pool. The juxtamembrane region surrounding FAs displays a gradient of FA plaque proteins with respect to both concentration and dynamics. Based on these findings, we propose a new model for the regulation of FA dynamics in which this juxtamembrane domain acts as an intermediary layer, enabling an efficient regulation of FA formation and reorganization.

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    • "Therefore, the cytosolic building blocks appear to be modules that are continuous along the functional axis of anchoring-mechanosensing-actin regulation and along the vertical axis across focal adhesions. Cell-matrix adhesion sites are dynamically maintained structures that constantly exchange their constituting material with the cytosol (Lele et al., 2008; Wolfenson et al., 2009). We pose here two alternative models for the mode of this exchange—symmetric and asymmetric (Figure 3A). "
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    ABSTRACT: eLife digest The space between the cells in a multi-cellular organism is filled with a structure called the extracellular matrix. The roles of this matrix vary from tissue to tissue, and include providing the cell with structural support and signalling cues. Cells use large multi-protein structures along their plasma membrane, called cell-matrix adhesion sites, to attach to the extracellular matrix and sense its properties. These sites are rapidly self-assembled upon local cues and are dynamically maintained by exchanging their components with the cytosol of the cell. Given the large number of different proteins that can be used to build adhesion sites, and the large number of possible interactions between these proteins, a major question is—how are these structures self-assembled both rapidly and correctly? Most research so far has concentrated on the adhesion sites themselves, as it has generally been assumed that their constituent proteins enter and leave these sites individually. However, using fluorescence techniques, Hoffmann et al. have now shown that these proteins are actually pre-assembled in the cytosol into small ‘building blocks’. These can make the construction of cell-matrix adhesion sites quicker and more accurate by reducing the number of steps in the self-assembly process. In addition, under most circumstances, these building blocks do not change when they are exchanged between the cytosol and the adhesion site: this means that they can be re-used repeatedly and accurately. The work of Hoffmann et al. also raises questions about whether similar principles govern the self-assembly of other large intracellular multi-protein structures. DOI: http://dx.doi.org/10.7554/eLife.02257.002
    eLife Sciences 06/2014; 3:e02257. DOI:10.7554/eLife.02257 · 8.52 Impact Factor
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    • "The EM studies revealed that the transmembrane interactions at focal adhesions are mediated via discrete particles of 25 nm in size that are attached to both the inner surface of the plasma membrane and the actin fibers. These results not only suggest that focal adhesions contain multiple ''hot spots'' of cytoskeletal anchorage (rather than a uniform protein mesh), but they also raise the possibility that differences in composition and molecular turnover may exist between the various particles within individual adhesions (Wolfenson et al., 2009b). In the superresolution iPALM studies (Kanchanawong et al., 2010), the z axis distribution of focal adhesion proteins was investigated, confirming that focal adhesions are laminated structures and that the integrins and actin inside focal adhesions are vertically bridged by a layer of plaque proteins composed of several subregions. "
    Developmental Cell 03/2013; 24(5):447-458. · 10.37 Impact Factor
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    • "The EM studies revealed that the transmembrane interactions at focal adhesions are mediated via discrete particles of 25 nm in size that are attached to both the inner surface of the plasma membrane and the actin fibers. These results not only suggest that focal adhesions contain multiple ''hot spots'' of cytoskeletal anchorage (rather than a uniform protein mesh), but they also raise the possibility that differences in composition and molecular turnover may exist between the various particles within individual adhesions (Wolfenson et al., 2009b). In the superresolution iPALM studies (Kanchanawong et al., 2010), the z axis distribution of focal adhesion proteins was investigated, confirming that focal adhesions are laminated structures and that the integrins and actin inside focal adhesions are vertically bridged by a layer of plaque proteins composed of several subregions. "
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    ABSTRACT: 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.
    Developmental Cell 03/2013; 24(5):447-58. DOI:10.1016/j.devcel.2013.02.012 · 10.37 Impact Factor
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