Kindlin

Kindlin refers to a small family of cytoplasmic proteins that regulate integrin activation and signaling. In vertebrates, three members have been identified: Kindlin-1 (encoded by FERMT1), Kindlin-2 (FERMT2), and Kindlin-3 (FERMT3). They display distinct tissue distribution: Kindlin-1 is enriched in epithelial tissues, Kindlin-2 is widely expressed, and Kindlin-3 is primarily found in hematopoietic cells.

All three proteins contain a conserved FERM domain that enables interactions with the cytoplasmic tails of beta integrins, a key step in converting integrins from inactive to active states. Kindlins function together with talin to regulate integrin activation and to organize signaling at focal adhesions and other adhesion structures. They influence outside-in and inside-out signaling, cytoskeletal organization, and cell adhesion and migration.

Biological roles of the kindlins include control of cell adhesion, motility, and tissue architecture during development, wound healing, and immune responses. Kindlin-3 is particularly important for platelet function and leukocyte adhesion, while Kindlin-1 and Kindlin-2 contribute to epithelial integrity and broader cellular adhesion processes.

Clinical significance is illustrated by specific genetic disorders. Mutations in FERMT1 cause Kindler syndrome, a rare autosomal recessive disorder characterized by skin fragility, photosensitivity, and blistering. FERMT3 mutations lead to a form of leukocyte adhesion deficiency (LAD-III), with impaired integrin activation causing bleeding and recurrent infections. Altered kindlin expression has also been observed in various cancers, where it can influence tumor cell adhesion and migration, though effects are context-dependent.

Kindlins are evolutionarily conserved regulators of integrin-mediated adhesion and signaling, integrating cytoskeletal dynamics with extracellular cues across diverse cell types.