Macrophage Migration and Phagocytosis Are Controlled by Kindlin-3's Link to the Cytoskeleton.

ABSTRACT: Major myeloid cell functions from adhesion to migration and phagocytosis are mediated by integrin adhesion complexes, also known as adhesome. The presence of a direct integrin binding partner Kindlin-3 is crucial for these functions, and its lack causes severe immunodeficiency in humans. However, how Kindlin-3 is incorporated into the adhesome and how its function is regulated is poorly understood. In this study, using nuclear magnetic resonance spectroscopy, we show that Kindlin-3 directly interacts with paxillin (PXN) and leupaxin (LPXN) via G43/L47 within its F0 domain. Surprisingly, disruption of Kindlin-3-PXN/LPXN interactions in Raw 264.7 macrophages promoted cell spreading and polarization, resulting in upregulation of both general cell motility and directed cell migration, which is

SUBMITTER: Liu H 

PROVIDER: S-EPMC8203317 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature