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Publication : Induction of STAP-1 promotes neurotoxic activation of microglia.

First Author  Stoecker K Year  2009
Journal  Biochem Biophys Res Commun Volume  379
Issue  1 Pages  121-6
PubMed ID  19100238 Mgi Jnum  J:144524
Mgi Id  MGI:3831067 Doi  10.1016/j.bbrc.2008.12.021
Citation  Stoecker K, et al. (2009) Induction of STAP-1 promotes neurotoxic activation of microglia. Biochem Biophys Res Commun 379(1):121-6
abstractText  Activated microglia contribute to neurodegenerative processes in the brain and the retina. Via DNA-microarray analysis, we have previously identified up-regulation of several immune-related genes in the dystrophic retina of retinoschisin-deficient (Rs1h(-/Y)) mice. Here we report a strong overexpression of transcripts for the signal-transducing adaptor protein-1 (STAP-1) in isolated Rs1h(-/Y) microglia. Furthermore, STAP-1 expression was induced in activated bone marrow-derived macrophages as well as LPS-, interferon-gamma-, and CpG-stimulated myeloid cell lines. Ectopic expression of STAP-1 in BV-2 microglia changed the morphology and cytoskeletal organization of the cells and transformed ramified cells to an activated state. STAP-1 overexpression also leads to an interaction with the M-CSF receptor/c-Fms diminishing its ligand-dependent phosphorylation. Finally, STAP-1 expressing cells showed strongly reduced migration with increased cytotoxicity against 661W photoreceptor like cells. Taken together, our study implicates a previously unknown role of STAP-1 in pro-inflammatory microglia activation potentially contributing to neuronal apoptosis and degeneration.
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