Benny Geiger's Lab

(In collaboration with Dr. Michal Sharon, Department of Biological Chemistry)

Focal adhesions are subcellular structures that anchor the cells to the extracellular matrix via integrin receptors and a multitude of associated adhesome proteins (Fig. 1, and http://www.adhesome.org). These interactions play a major role in cellular morphogenesis, cell migration and adhesion-mediated environmental sensing. Thirty years of research in the fields of cytoskeleton and cell-matrix interactions have uncovered the involvement of more than 180 proteins, which form a network of over 700 interactions, in the adhesive process. However, despite the massive amount of knowledge gathered so far regarding the components of these subcellular adhesion sites, little is known about their molecular architecture. Recent advances in the field suggest the existence of a small, dynamic set of adhesion-related protein complexes. In this work, these protein complexes are isolated, utilizing native mass spectrometry in conjunction with cell biology and microscopy.

Figure 1: The integrin adhesome network. This network is divided here into structural (center) and regulatory/signaling (left and right) sub-networks. The structural part consists of actin, integrins (ITGA, ITGB) and other adhesion receptors (light brown ellipses), cytoskeletal proteins (cyan), actin modulators (light green) and multi-domain adaptor proteins (red). The regulatory/signaling part includes small GTPase proteins and their activators and inhibitors (blue hexagons, rectangles and ellipses, respectively), tyrosine kinases and phosphatases (orange rectangles and ellipses), serine/threonine kinases and phosphatases (yellow rectangles and ellipses), phospholipids and their kinases, phosphatases and lipases (pink hexagons, rectangles, ellipses and diamonds), chaperones and mediators of protein degradation (black and grey), and transcription factors (sky blue). Integrin adhesome data is largely based on Zaidel-Bar and Geiger, Journal of Cell Science 123 (2010), pp1385-1388; and http://www.adhesome.org.
 

From Zamir E and Geiger B. Focal adhesions and related integrin contacts. Encyclopedia of Biological Chemistry, 2^nd Edition (2010)