Direct α_IIbβ₃-cytoskeletal coupling. A number of proteins permit direct coupling of integrins to the actin cytoskeleton, which is important in platelets for processes such as clot retraction. However, the current understanding of this coupling is limited in platelets relative to other cell types. Talin can provide a direct link between the β₃-integrin C-terminal tail and actin, and has been reported to be important for clot retraction. Stretch-induced changes in talin lead to the exposure of binding sites for vinculin, although the role for this protein in platelet α_IIbβ₃ signaling may be minimal. Paxillin and α-actinin can associate with the α_IIbβ₃ C-terminal tails, and may regulate integrin affinity and actin coupling. Kindlin-3 can couple directly to β₃ integrins, and to the actin cytoskeleton via the heterotrimeric complex of ILK, PINCH, and Parvin. ILK can itself couple directly to β₃ integrins, and also acts as a scaffold to recruit further proteins. Myosin can bind directly to the tyrosine-phosphorylated β₃ C-terminal tail. It is important to note that the integrin-binding sites for many of the depicted proteins may overlap (see “Proteins enabling more direct integrin-cytoskeleton coupling” and Figure 6). The α_IIbβ₃ adhesome is likely to involve a number of further proteins permitting direct coupling of the integrin to the actin cytoskeleton, which are yet to be identified.