Search

Talin (herein referring to the talin-1 form), is a cytoskeletal adapter protein that binds integrin receptors and F-actin, and is a key factor in the formation and regulation of integrin-dependent cell–matrix adhesions. Talin forms the mechanical link between the cytoplasmic domain of integrins and the actin cytoskeleton. Through this linkage, talin is at the origin of mechanosignaling occurring at the plasma membrane–cytoskeleton interface. Despite its central position, talin is not able to fulfill its tasks alone, but requires help from kindlin and paxillin to detect and transform the mechanical tension along the integrin–talin–F-actin axis into intracellular signaling. The talin head forms a classical FERM domain, which is required to bind and regulate the conformation of the integrin receptor, as well as to induce intracellular force sensing. The FERM domain allows the strategic positioning of protein–protein and protein–lipid interfaces, including the membrane-binding and integrin affinity-regulating F1 loop, as well as the interaction with lipid-anchored Rap1 (Rap1a and Rap1b in mammals) GTPase. Here, we summarize the structural and regulatory features of talin and explain how it regulates cell adhesion and force transmission, as well as intracellular signaling at integrin-containing cell–matrix attachment sites.

Integrins are cellular receptors that regulate cell adhesion and many other cellular functions. Integrins can be activated via an “inside-out pathway” that is promoted by RAP1 GTPase. RAP1-GTP-Interacting Adaptor Molecular (RIAM) mediates integrin activation by linking RAP1 GTPase to talin, an integrin activator. RIAM’s function in integrin signaling is tightly regulated. In this commentary, we review recent studies of the molecular mechanisms underlying RIAM autoinhibition via both intramolecular interaction and oligomer assembly, and the phosphorylation-dependent activation of RIAM.

Planar cell polarity is a fundamental process during embryogenesis comprising of uniform polarization of cells and coordinated cell migration events. These events are critical in shaping the three-dimensional body plan of a living organism. Defects in these events are associated in various developmental anomalies. The molecular mechanism by which these cells polarize for directional migration remains elusive. In this chapter, we discuss our understanding regarding the molecular control and functional mechanisms of the global clue in establishing planar cell polarity during embryonic development.