Purpose of review: The modulation of integrin affinity is central to platelet and leukocyte function. Two proteins, talin and kindlin, that interact with distinct regions of integrin cytoplasmic domains, have been shown to play essential roles in inducing the high affinity integrin conformation required for platelet and leukocyte adhesive interactions.Here we highlight some of the key studies that have described roles for talin and kindlin in integrin function and discuss several models that explain how talin and kindlins might work together to regulate integrin activation.
Recent findings: Genetic deletion of kindlin-3 in mice results in platelet and leukocyte adhesive dysfunction associated with profoundly impaired activation of multiple classes of integrins, a phenotype similar to that observed in talin-deficient platelets and leukocytes. Since this initial report three years ago, numerous studies have provided important clues to how kindlins activate integrins and, in some cases, the relationship between kindlins and talin in integrin activation.
Summary: Clearly, talin and kindlins are key regulators of integrin affinity. Future experiments that define precisely how these molecules work in concert should provide important insights into the terminal signaling events that activate integrins.