Transport of the leaderless protein Ku on the cell surface of activated monocytes regulates their migratory abilities.
Recent evidence shows that the DNA repair protein Ku is expressed on the surface of a subset of cells, where it contributes to adhesion and invasion processes, and also to viral or bacterial entry into target cells. Here, we show that Ku was expressed on the cell surface during activation of human monocytes and that its expression was independent of the conventional endoplasmic reticulum (ER)/Golgi secretory pathway. Ku inhibition, by blocking antibodies, decreases the migration of monocytes on fibronectin and laminin. On activation, nuclear Ku seems to move to the periphery of the cell and it shows a punctuate staining in the cytoplasm. The cytoplasmic distribution of Ku was shown to be unaltered by brefeldin A. Protease protection experiments show that Ku is contained within vesicles in activated monocytes. These data support a new role for Ku in the migration of monocytes into tissues, which depends on a tightly regulated pathway of intracellular redistribution.
Paupert
Jenny
J
Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, 205 Route de Narbonne, 31077 Toulouse cedex, France.
Dauvillier
Stéphanie
S
Salles
Bernard
B
Muller
Catherine
C
D034961:Antigens, Nuclear / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D000072200:Ku Autoantigen; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D021382:Protein Sorting Signals; D021381:Protein Transport / Q000187:drug effects; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D021382:Protein Sorting Signals; D016173:Macrophage Colony-Stimulating Factor; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen