Date of Award


Degree Type




First Advisor

Plow, Edward

Subject Headings

Biomolecules -- Structure, Nuclear magnetic resonance, Integrins, Structural biology, NMR, Integrin, Filamin, Cell migration


Cell functions in multi-cellular organisms are strongly depend on the dynamic cooperation between cell adhesion and cytoskeleton reorganization. Integrins, the major cell adhesion receptors, bind to extracellular matrix (ECM) and soluble ligands on the cell surface and link to the actin cytoskeleton inside the cell membrane. In this manner, integrins integrate cell adhesion and cytoskeleton reorganization by acting as a mechanical force transducer and a biochemical signaling hub (Zamir and Geiger 2001). Consequently, integrins are vital for development, immune responses, leukocyte traffic and hemostasis, and a variety of other cellular and physiological processes. Integrins are also are the focal point of many human diseases, including genetic, autoimmune, cardiovascular and others. In terms of the cell-ECM adhesion, integrins can exist in two major states, active, where it binds to appropriate extracellular ligands, and inactive, where it disassociates from extracellular ligands. The cellular pathways that modify the integrin extracellular ligand binding states have been called inside-out integrin signaling while the pathways that are mediated by the extracellular binding have been called outside-in integrin signaling. Although the directions of outside-in and inside-out signaling point to each other, they often happen reciprocally. Rather than just integrins alone accomplishing integrin signaling, numerous proteins are recruited around integrins and are limited to the clearly defined range of focal adhesion that are large molecular complexes containing >100 proteins which link integrins to cytoskeleton (Figure 1) (Zaidel-Bar et al. 2004). Proteins that directly interact with integrins are crucial for understanding integrin signaling. More importantly, proteins that link integrins to the cytoskeleton are responsible for both mechanical forces and biochemical signal transduction, as well as reorganizing the cytoskeleton. Moreover, the modification of integrin ligand binding states is dependent on the linkage to

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Chemistry Commons