Miro-1 links mitochondria and microtubule Dynein motors to control lymphocyte migration and polarity.
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.
Vascular Biology and Inflammation Department, Centro Nacional Investigaciones Cardiovasculares, Madrid, Spain.
Giulia
G
Morlino
Olga
O
Barreiro
Francesc
F
Baixauli
Javier
J
Robles-Valero
José M
JM
González-Granado
Ricardo
R
Villa-Bellosta
Jesús
J
Cuenca
Carlos O
CO
Sánchez-Sorzano
Esteban
E
Veiga
Noa B
NB
Martín-Cófreces
Francisco
F
Sánchez-Madrid
D002465:Cell Movement / Q000502:physiology; D016764:Cell Polarity / Q000276:immunology / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D004398:Dyneins / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D008870:Microtubules / Q000276:immunology / Q000378:metabolism*; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D054377:Chemokine CXCL12; D016023:Integrins; D024101:Mitochondrial Proteins; C473124:RHOT1 protein, human; D004398:Dyneins; D020741:rho GTP-Binding Proteins