Talin mediates monocyte α4β1 integrin‐mediated migration, but not chemokine‐triggered α4β1 affinity up‐regulation or adhesion

Abstract

α4β1 integrin plays an important role in monocyte adhesion and emigration. Activation by chemokines and chemoattractants is required to increase α4β1 integrin affinity and mediate adhesion to VCAM‐1 expressed by cytokine‐activated endothelium. We investigated the role of talin, a cytoskeletal protein that interacts with integrin cytoplasmic tails, in α4β1 integrin‐dependent functions using formyl peptide receptor‐transfected U937 monocytic cells. fMLP‐induced affinity up‐regulation, measured by binding of soluble LDV‐FITC peptide, was unaffected by siRNA knockdown of talin‐1 or sequestration of talin through expression of a dominant inhibitory talin‐binding fragment of phosphatidylinositol phosphate kinase type I‐90. Similarly, talin‐1 knockdown did not inhibit fMLP or SDF‐1‐stimulated adhesion to VCAM‐1. Talin was however, essential for PMA‐induced adhesion to VCAM‐1, but not PMA‐induced α4β1 integrin affinity up‐regulation. In addition, talin knockdown reduced fMLP‐driven, α4β1 integrin‐dependent chemotactic migration across VCAM‐1 coated filters.These results suggest that talin association with the cytoplasmic tail of α4β1 integrin is not involved in chemokine‐induced affinity changes or adhesion. However, talin plays an important role in α4β1 integrin‐mediated chemotactic migration and PMA‐induced adhesion to VCAM‐1, steps that follow affinity modulation. Funded by CIHR.