Induction of STAP-1 promotes neurotoxic activation of microglia.
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.
Stoecker
Katharina
K
Institute of Human Genetics, University of Regensburg, Regensburg, Germany.
Weigelt
Karin
K
Ebert
Stefanie
S
Karlstetter
Marcus
M
Walczak
Yana
Y
Langmann
Thomas
T
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D000818:Animals; D017209:Apoptosis; D015815:Cell Adhesion Molecules / Q000235:genetics; D002633:Chemotaxis; D005136:Eye Proteins / Q000235:genetics; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages; D051379:Mice; D008817:Mice, Mutant Strains; D017628:Microglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis; D012173:Retinitis / Q000378:metabolism* / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D005136:Eye Proteins; C491843:RS1 protein, mouse; C534885:STAP-1 protein, mouse; D009569:Nitric Oxide; D016173:Macrophage Colony-Stimulating Factor