Induction of STAP-1 promotes neurotoxic activation of microglia

Stoecker, Katharina and Weigelt, Karin and Ebert, Stefanie and Karlstetter, Marcus and Walczak, Yana and Langmann, Thomas (2009) Induction of STAP-1 promotes neurotoxic activation of microglia. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 379 (1). pp. 121-126. ISSN 0006-291X, 1090-2104

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Abstract

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) MiCFOglia. 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. (C) 2008 Elsevier Inc. All rights reserved.

Item Type: Article
Uncontrolled Keywords: RETINOSCHISIN-DEFICIENT RETINA; MOLECULAR-CLONING; ADAPTER PROTEIN; KINASE; CELLS; EXPRESSION; PHENOTYPE; BRDG1; Microglia; Adaptor protein; Migration; Phagocytosis; c-Fms; NO secretion; Photoreceptors; Neurotoxicity; Apoptosis
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Humangenetik
Depositing User: Dr. Gernot Deinzer
Date Deposited: 07 Oct 2020 08:19
Last Modified: 07 Oct 2020 08:19
URI: https://pred.uni-regensburg.de/id/eprint/29562

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