STAT3-stathmin interactions control microtubule dynamics in migrating T-cells.
T-cell migration is a complex highly coordinated process that involves cell adhesion to the high endothelial venules or to the extracellular matrix by surface receptor/ligand interactions, cytoskeletal rearrangements, and phosphorylation-dependent signaling cascades. The mechanism(s) that regulates T-cell migration is of considerable relevance for understanding the pathogenesis of various diseases, such as chronic inflammatory diseases and cancer metastasis. This study was designed to identify potential involvement of STAT3, a latent transcription factor, in mediating integrin-induced T-cell migration. Using our previously characterized in vitro model for lymphocyte migration, we demonstrate that STAT3 is activated and translocated to the nucleus during the process of active motility of Hut78 T-lymphoma cells triggered via LFA-1. Blocking STAT3 signaling by multiple approaches inhibited LFA-1-induced T-cell locomotion via destabilization of microtubules and post-translational modification of tubulin. Here, we show that STAT3 physically interacts with stathmin to regulate microtubule dynamics in migrating T-cells. These observations strongly indicate that STAT3 is critically important for T-cell migration and associated signaling events.
Verma
Navin K
NK
Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Dublin 8, Ireland. verman@tcd.ie
Dourlat
Jennifer
J
Davies
Anthony M
AM
Long
Aideen
A
Liu
Wang-Qing
WQ
Garbay
Christiane
C
Kelleher
Dermot
D
Volkov
Yuri
Y
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D050777:Stathmin / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050777:Stathmin; D014404:Tubulin