kindlins

Kindlins are a small family of cytoplasmic proteins that regulate integrin activation and signaling. In mammals, three genes encode kindlin proteins: FERMT1 (kindlin-1), FERMT2 (kindlin-2), and FERMT3 (kindlin-3). They share a FERM domain-containing structure and localize to focal adhesions and the cell cortex, where they participate in adhesion and cytoskeletal organization.

Kindlins bind to the cytoplasmic tails of beta integrins through their F3 subdomain of the FERM domain, and they act in conjunction with talin to promote the high-affinity, active conformation of integrins. They also participate in signaling networks that regulate actin remodeling and cell spreading, migration, and outside–in signaling.

Expression patterns vary: Kindlin-1 is abundant in stratified epithelia; Kindlin-2 is ubiquitous with roles in development and tissue remodeling; Kindlin-3 is enriched in hematopoietic cells and platelets and is critical for immune cell adhesion. Genetic ablation in model organisms demonstrates essential roles in development; tissue-specific knockouts reveal contributions to wound healing, angiogenesis, and cancer cell motility.

Mutations in FERMT1 cause Kindler syndrome, characterized by skin fragility, photosensitivity and mucosal involvement. FERMT3 mutations cause a leukocyte adhesion deficiency type III syndrome, with impaired integrin activation leading to immunodeficiency and bleeding tendencies. Some studies link altered kindlin expression to cancer progression and metastasis, though the functional context is ongoing.

Overall, kindlins are key components of the integrin activation machinery, acting as co-activators with talin to regulate cell adhesion and signaling in diverse tissues.