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. |