Correlation Engine 2.0
Clear Search sequence regions


Sizes of these terms reflect their relevance to your search.

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 in a drastic contrast to the consequences of Kindlin-3 knockout. Moreover, disruption of Kindlin-3-PXN/LPXN binding promoted the transition from mesenchymal to amoeboid mode of movement as well as augmented phagocytosis. Thus, these novel links between Kindlin-3 and key adhesome members PXN/LPXN limit myeloid cell motility and phagocytosis, thereby providing an important immune regulatory mechanism. Copyright © 2020 by The American Association of Immunologists, Inc.

Citation

Huan Liu, Liang Zhu, Tejasvi Dudiki, Benjamin Gabanic, Logan Good, Eugene A Podrez, Olga A Cherepanova, Jun Qin, Tatiana V Byzova. Macrophage Migration and Phagocytosis Are Controlled by Kindlin-3's Link to the Cytoskeleton. Journal of immunology (Baltimore, Md. : 1950). 2020 Apr 01;204(7):1954-1967

Expand section icon Mesh Tags

Expand section icon Substances


PMID: 32094207

View Full Text