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Induction of STAP-1 promotes neurotoxic activation of microglia.

Stoecker K., Weigelt K., Ebert S., Karlstetter M., Walczak Y., Langmann T.

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.

Biochem. Biophys. Res. Commun. 379:121-126(2009) [PubMed] [Europe PMC]

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