Macrophage Migration and Phagocytosis Are Controlled by Kindlin-3's Link to the Cytoskeleton
| Autor: | Liang Zhu, Eugene A. Podrez, Benjamin Gabanic, Jun Qin, Tejasvi Dudiki, Huan Liu, Tatiana V. Byzova, Olga A. Cherepanova, Logan Good |
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| Rok vydání: | 2019 |
| Předmět: |
Phagocytosis
Immunology Integrin Motility Article Cell Line 03 medical and health sciences Mice 0302 clinical medicine Cell Movement Immunology and Allergy Macrophage Animals Humans Paxillin Cytoskeleton Integrin binding Binding Sites biology Adhesome Chemistry Macrophages Membrane Proteins Cell migration Phosphoproteins Cell biology Neoplasm Proteins Cytoskeletal Proteins HEK293 Cells RAW 264.7 Cells biology.protein NIH 3T3 Cells 030215 immunology Protein Binding |
| Zdroj: | J Immunol |
| ISSN: | 1550-6606 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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