Macrophage Migration and Phagocytosis Are Controlled by Kindlin-3's Link to the Cytoskeleton.
J Immunol
; 204(7): 1954-1967, 2020 04 01.
Article
em En
| MEDLINE
| ID: mdl-32094207
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 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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fagocitose
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Citoesqueleto
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Movimento Celular
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Macrófagos
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Proteínas de Membrana
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Proteínas de Neoplasias
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2020
Tipo de documento:
Article