Structural Investigation of the Complex of Filamin A Repeat 21 with Integrin αIIb and β3 Cytoplasmic Tails – A Potential “Transmission” to Regulate 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