Induction of STAP-1 promotes neurotoxic activation of microglia
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- 作者：Katharina Stoecker ; Karin Weigelt ; Stefanie Ebert ; Marcus Karlstetter ; Yana Walczak ; Thomas Langmann
- 关键词：Microglia ; Adaptor protein ; Migration ; Phagocytosis ; c-Fms ; NO secretion ; Photoreceptors ; Neurotoxicity ; Apoptosis
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2009
- 出版时间：30 January 2009
- 年：2009
- 卷：379
- 期：1
- 页码：121-126
- 全文大小：383 K
文摘
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-γ-, 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.