Kim et al. show how the cytoskeletal adaptor protein talin activates integrins.
Activating integrins, or making them stickier, helps control cell migration and adhesion and construction of the extracellular matrix. Researchers know that activation involves the protein talin, which clamps onto the cytoplasmic tail of the β subunit of an integrin. But they aren't certain how that interaction alters the adhesiveness of the integrin's extracellular end. One possibility is that talin attachment tilts the membrane-spanning domain of the β subunit, separating the transmembrane portions of the β and α subunits and switching the integrin on. Alternatively, talin might induce a piston-like motion, pushing the transmembrane domain farther out or retracting it.
Kim et al. tested these two explanations by implanting the membrane-spanning section of the β3 integrin into tiny membrane “nanodiscs.” To determine whether talin caused tilting or sliding, they attached a fluorophore to the intracellular or extracellular end of the fragment. The more hydrophobic its surroundings, the brighter the fluorophore glows. Talin attachment increased the glow from a fluorophore linked to the extracellular tip, indicating that this end of the fragment sinks into the membrane. After talin binding, a fluorophore attached to the cytoplasmic end of the transmembrane domain also shone brighter. Thus, both ends of the fragment bury themselves in the membrane, suggesting that talin binding alters the angle of the β subunit rather than causing a piston-like movement. However, the researchers caution that they can't rule out the possibility that talin binding rotates rather than tilts the β integrin.