Posttranslational modification of b1A integrin, its impact on kindlin-2 adaptor protein binding and cell matrix adhesion

Analysis of the interaction between the b1 integrin tail with the adaptor protein kindlin and its regulation by posttranslational modification; impact on cell adhesion, migration and fibronectin fibrillogenesis:

Overview

Mutations in a5b1A and a7b1D integrins lead to muscular dystrophies, showing their physiological importance for cell adhesion to the extracellular matrix. Despite their critical role, the mechanisms that regulate intracellular adapter protein recruitment and the respective control of integrin-dependent formation of fibronectin fibrils in the extracellular matrix are still unknown.

Aim

In this project, I would like to study the interaction of the b1 integrin cytoplasmic tail with the adapter protein kindlin, establish how posttranslational modification of the integrin receptor influences kindlin-binding affinity; and thereby establish the physiological role of integrins in cell adhesion, migration and fibronectin fibrillogenesis. With the help of mutagenesis and biochemical and cell biological experiments, I will investigate the mutual protein interactions and how differential adapter-binding influences integrin-dependent functions.