Miro-1 links mitochondria and microtubule Dynein motors to control lymphocyte migration and polarity

[EN]The recruitment of leukocytes to sites of inflammation is crucial for a functional immune response. In the present work, we explored the role of mitochondria in lymphocyte adhesion, polarity, and migration. We show that during adhesion to the activated endothelium under physiological flow condit...

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Detalhes bibliográficos
Autores: Morlino, Giulia, Barreiro, Olga, Baixauli, Francesc, Robles Valero, Javier, González-Granado, José M, Villa-Bellosta, Ricardo, Cuenca, Jesús, Sánchez-Sorzano, Carlos O, Veiga, Esteban, Martín-Cófreces, Noa B, Sánchez-Madrid, Francisco
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Recursos:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/168642
Acesso em linha:http://hdl.handle.net/10366/168642
Access Level:acceso abierto
Palavra-chave:Mitochondria
T cell activation and migration
Miro-1
Microtubules
Cell Polarity
Cell Movement
Signal Transduction
Cytoskeleton
Integrins
rho GTP-Binding Proteins
Dyneins
Lymphocytes
2415 Biología Molecular
microtúbulos
citoesqueleto
movimiento celular
mitocondrias
transducción de señales
dineínas
polaridad celular
linfocitos
integrinas
proteínas de unión al GTP rho
Descrição
Resumo:[EN]The recruitment of leukocytes to sites of inflammation is crucial for a functional immune response. In the present work, we explored the role of mitochondria in lymphocyte adhesion, polarity, and migration. We show that during adhesion to the activated endothelium under physiological flow conditions, lymphocyte mitochondria redistribute to the adhesion zone together with the microtubule-organizing center (MTOC) in an integrin-dependent manner. Mitochondrial redistribution and efficient lymphocyte adhesion to the endothelium require the function of Miro-1, an adaptor molecule that couples mitochondria to microtubules. Our data demonstrate that Miro-1 associates with the dynein complex. Moreover, mitochondria accumulate around the MTOC in response to the chemokine CXCL12/SDF-1α; this redistribution is regulated by Miro-1. CXCL12-dependent cell polarization and migration are reduced in Miro-1-silenced cells, due to impaired myosin II activation at the cell uropod and diminished actin polymerization. These data point to a key role of Miro-1 in the control of lymphocyte adhesion and migration through the regulation of mitochondrial redistribution.