Dynamic regulation of the structure and functions of integrin adhesions

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.

Figure 1. Diversity of Integrin-Mediated Cell Matrix Adhesion Structures as Viewed by Different Microscopy Techniques

(A)A transmission electron microscope (TEM) image of chicken lens cells in culture. The black arrow indicates a focal adhesion.(B) A cryo-EM image of chicken gizzard smooth muscle. Arrows indicate focal adhesions sites.(C) Focal adhesions (arrows) and focal complexes (arrowheads) formed by a human foreskin fibroblast stained for paxillin (red) and actin (green). (D) Fibrillar adhesions (arrows) formed by a WI38 human lung fibroblast, stained for tensin (red) and fibronectin (green). (E) Podosomes forming a “sealing zone” in a cultured osteoclast derived from murine bone marrow, stained for paxillin (red) and actin (green). (F) Invadopodia (arrows) formed by an A375 metastatic melanoma cell stained for vinculin (green) andTKS5(red). Images in (A) and (B) were provided by Ilana Sabanay; images in (C) and (D) were provided by TovaVolberg; image in (E) was provided by Chen Luxenburg; image in (F) was provided by Or-Yam Shoshana.

Figure 2. Molecular Complexity of Focal Adhesions

(A) Interactions between functional families of adhesome molecules. The various components of the adhesome form two major groups: scaffolding molecules and regulatory molecules. These groups have been further subdivided, according to the known biological activities of the different components. The dominant interactions between families (red arrows, activating interactions; blue arrows, inhibiting interactions; black lines, binding interactions) are shown (modified from Zaidel-Bar et al., 2007a). (B) To illustrate the complex molecular composition of focal adhesions, a HeLa cell was immunolabeled for three different adhesion components: ILK, zyxin, and actin. The merged image highlights the distinct localization of the different proteins within the same structures.

Figure 3. Molecular and Structural Kinetics of Focal Adhesions

(A) Structural dynamics of focal adhesions. A HeLa cell expressing GFP-vinculin was recorded for 12 min by time-lapse fluorescence microscopy. The resulting images were analyzed by temporal ratio imaging (bottom right image), enabling comparison of the same structure sat different time points. Are d shift denotes structures with decreased intensity; a blue shift denotes an increase in intensity; green and yellow hues mark unchanged pixels. (B) Different focal adhesion proteins display varying turnover rates. Normalized averaged curves of FRAP experiments performed in HeLa cells on different GFP-tagged adhesion-related proteins are shown. In each case, an average of 20–30 FRAP curves is displayed. Note the different timescales of the measurements, as well as the half-time to full recovery (T_1/2)values.