Intracellular signaling in M‐CSF‐induced microglia activation: Role of Iba1

Abstract

Microglia are reactively activated by various environmental stimulations caused by brain injury or disease. Activated microglia exhibit morphological transformation, proliferation, migration, phagocytosis, and the production of bioactive molecules. Various molecules are reported and suggested to activate microglia. Among them, macrophage-colony-stimulating factor (M-CSF) is considered one of the most convincing candidates responsible for maintaining activation properties of microglia. Therefore, the focus of the present study is on intracellular molecular events that arise downstream of M-CSF stimulation. M-CSF activates its receptor, Fms tyrosine kinase, and Fms sequentially activates a number of signaling molecules, including PI3K or phospholipase C␥ (PLC␥). Stimulation of continuing signaling cascades results in the activation of a small GTPase, Rac, the key molecule in microglia activation. Rac is known to be activated downstream of receptor tyrosine kinases and to regulate reorganization of the actin cytoskeleton, which profoundly underlies the above-mentioned properties of activated microglia. Iba1, a macrophage/microglia-specific calcium-binding protein, was identified by our group and was shown to be involved in the Rac signaling pathway. Further, we introduce a novel signaling pathway in which Rac is activated, dependent on PLC␥ and Iba1. However, to understand the molecular details of microglia activation, future work is required. GLIA 40: 164 -174, 2002.

Loss of Allograft Inflammatory Factor-1 Ameliorates Experimental Autoimmune Encephalomyelitis by Limiting Encephalitogenic CD4 T-Cell Expansion

“…Interestingly, the effect of Aif-1 deficiency on leukocyte populations after immunization was relatively modest, with a decrease of ~10% in the number of both CD3 the cytoplasm, and molecular functions ascribed to Aif-1 to date include actin bundling activity (35); it has also been linked to signaling via the small GTPase Rac (36,37), which itself is well known to affect actin cytoskeletal dynamics (38). The Aif-1 protein structure is notable for a conserved EF hand motif, although there are conflicting reports as to whether this is capable of binding Ca 2+ (39,40).…”

Delayed neuronal cell death in brainstem after transient brainstem ischemia in gerbils

“…Expression of IBA-1 is mostly limited to the monocyte/macrophage lineage, and is augmented by cytokines such as IFN-γ. It was assumed that IBA-1 is a novel molecule involved in inflammatory responses and allograft rejection, as well as activation of macrophages [22]. In the normal brain, IBA-1 is highly expressed in resident microglial cells, but is never expressed in neurons and astrocytes [22].…”

“…It was assumed that IBA-1 is a novel molecule involved in inflammatory responses and allograft rejection, as well as activation of macrophages [22]. In the normal brain, IBA-1 is highly expressed in resident microglial cells, but is never expressed in neurons and astrocytes [22]. After ischemia, IBA-1 is also expressed in activated resident microglial cells and infiltrating hematogenous macrophages [23,24].…”

Neurotoxic Effects of Lipopolysaccharide on Nigral Dopaminergic Neurons Are Mediated by Microglial Activation, Interleukin-1β, and Expression of Caspase-11 in Mice

“…The rabbit polyclonal anti-tyrosine hydroxylase (TH) antibody was purchased from Calbiochem-Novabiochem Corp. (San Diego, CA). The rabbit polyclonal antibody against Iba1, a microglia/macrophage-specific calcium-binding protein (11), was kindly provided by Dr. Shinichi Kohsaka from the National Institute of Neuroscience (Tokyo, Japan). The rat monoclonal anti-caspase-11 antibody was a gift from Prof. J. Yuan (10).…”