CRC TRR 332 - C01: Role of α-actinin in neutrophil recruitment and neutrophil effector function

Basic data for this project

Description

In order to leave the vessel at sites of tissue damage and inflammation, leukocytes have to interact with the endothelium prior transmigration into inflamed tissues. Integrins are required for leukocyte recruitment and functions and the actin cytoskeleton plays a central role in immune cell formation and function. The F-actin-binding proteins talin, α-actinin, and filamin bind integrin cytoplasmic tails as well as other cytoskeletal or scaffold proteins, and mediate the attachment of integrins to actin filaments. However, the complex mechanisms underlying integrin–cytoskeletal linkage regulation remain to be elucidated. α-Actinins (ACTN) are actin filament crosslinking proteins and leukocytes exclusively express ACTN1 and 4. We specifically investigate the role of ACTN1 in integrin activation and neutrophil activation and function. We investigate the role of ACTN1 in inflammation in clinically relevant disease models and how ACTN1 in neutrophils is involved in integrin activation and neutrophil recruitment. Furthermore, we study if ACTN1 is also involved in neutrophil antimicrobial effector functions mediated by integrin outside-in signalling.