Regulation of integrin-dependent adhesions by the kindlin-talin interplay

Integrins are cell surface receptors that allow the cell to interact with the extracellular matrix (ECM). Being connected to both the external environment and the cytoskeleton of the cell, integrins play a crucial role in the transmission of forces and mechanical signals from inside and outside of the cell.

Integrin activation requires binding to an ECM ligand and the recruitment of adapters within their cell. Mandatory adapters like talin and kindlin are recruited to the β-integrin cytoplasmic domain to anchor integrins to the actin cytoskeleton and to stabilize the receptor/adapter complex within the focal adhesions. Despite the neighboring binding sites of talin and kindlin on the integrin tail, whether they can reciprocally stabilize their respective binding to the integrin is not understood.

Using Alphafold2 models, I'm investigating the potential interactions between talin and kindlin. My current data supports the hypothesis of an interaction between these two adapters. In the future, this complex could be purified and observed by cryo-electron microscopy to confirm these interactions.