Novel Cytoskeletal Regulator discovered
The T Cell Signal Transduction Group of the Molecular Immunology Unit discovered with research partners from Erlangen how T cells control via the cytokine interferon-gamma cytoskeleton-dependent cellular responses.
Interferon-gamma is produced by natural killer cells and subpopulations of T cells (CD4+ Th1 cells, CD8+ cytotoxic T cells and natural killer T cells). Interferon-gamma is a major defense factor against viral and intracellular bacterial infections and tumors. Cells stimulated by interferon-gamma rapidly express in the cytoplasm guanylate binding protein 1 (GBP-1), which is with a molecular weight of 67-kDa a member of the large G-protein family.
The research group identify as physical and functional GBP-1 interaction partners the cytoskeleton protein actin, further plastin-2 that bundles actin fibers and spectrin b-chain-brain 1 that links the plasma membrane to the actin cytoskeleton.
The researcher found further that GBP-1 regulates via the interaction with these molecules the cytoskeleton that results for instance in control of cell spreading and cell motility and in T cells also in regulation of surface expression of the T cell antigen receptor and the leukocyte phosphatase CD45.
In conclusion, the research group discovered GBP-1 as a central immunoregulatory component and thus as a novel therapeutic target for immune diseases and cancer.
The work was recently published in Molecular and Cellular Biology and The Journal of Immunology:
Ostler, N., N. Britzen-Laurent, A. Liebl, E. Naschberger, G. Lochnit, M. Ostler, F. Forster, P. Kunzelmann, S. Ince, V. Supper, G. Praefcke, D. Schubert, H. Stockinger, C. Herrmann, and M. Stürzl. 2014. IFN-γ-induced Guanylate Binding Protein-1 is a novel actin cytoskeleton remodeling factor. Mol. Cell. Biol. 34: 196.
Forster, F., W. Paster, V. Supper, P. Schatzlmaier, S. Sunzenauer, N. Ostler, A. Saliba, P. Eckerstorfer, N. Britzen-Laurent, G. J. Schütz, J. A. Schmid, G. J. Zlabinger, E. Naschberger, M. Stürzl, and H. Stockinger. 2014. GBP-1 mediated interaction of the T-cell antigen receptor signaling with the cytoskeleton. J. Immunol. 192: 771.
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