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 Cgamma (PLCgamma). 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 PLCgamma and Iba1. However, to understand the molecular details of microglia activation, future work is required.
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MCSF signaling activates its receptor FMS tyrosine kinase, which sequentially activates PI-3 kinase and Rac in microglia and bone marrow derived cells.
“existing literature provides evidence that MCSF signaling activates its receptor the FMS tyrosine kinase which sequentially activates PI-3 kinase and Rac in microglia and bone marrow derived cells [48], [49].”
From Rac2 Controls Tumor Growth, Metastasis and M1-M2 Macrophage Differentiation In Vivo (2014) · cites this paper as [48]
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Rac2 Controls Tumor Growth, Metastasis and M1-M2 Macrophage Differentiation In Vivo
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“In support of our results, existing literature provides evidence that MCSF signaling activates its receptor the FMS tyrosine kinase which sequentially activates PI-3 kinase and Rac in microglia and bone marrow derived cells [48,49].”
ResultSmith, A. M., Gibbons, H. M., Oldfield, R. L., Bergin, P. M., Mee, E. W., Curtis, M. A., Faull, R. L. M., & Dragunow, M. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-85 · Cited by 107 · see citing works
The Alzheimer’s disease-associated protective Plcγ2-P522R variant promotes immune functions
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Tang, M.-M., Lin, W.-J., Pan, Y.-Q., & Li, Y.-C. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00255 · Cited by 73 · see citing works
“We stained the sections of hippocampus with Iba1, the identification marker of microglia (Imai and Kohsaka, 2002; Yirmiya et al., 2015).”
MethodLee, H.-L., Jung, K.-M., Fotio, Y., Squire, E., Palese, F., Lin, L., Torrens, A., Ahmed, F., Mabou Tagne, A., Ramirez, J., et al. (2022) · Biological Psychiatry · doi:10.1016/j.biopsych.2022.04.017 · Cited by 38 · see citing works
Xia, Y., Chen, C., Chen, J., Hu, C., Yang, W., Wang, L., Liu, L., Gao, L.-P., Wu, Y.-Z., Chen, D.-D., et al. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02989-y · Cited by 7 · see citing works
- Authors
- Imai, Y., & Kohsaka, S.
- Affiliations
- National Institute of Neuroscience (JP)
- Corresponding author
- Kohsaka, Shinichi
- ORCID
- Kohsaka, Shinichi
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2002-10-04
- Volume
- 40
- Issue
- 2
- Pages
- 164-174
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W2082755707
- Cited by
- 359
- References
- 7
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 12 · 2023: 11 · 2022: 18 · 2021: 20 · 2020: 28 · 2019: 17 · 2018: 24 · 2017: 19 · 2016: 21 · 2015: 16 · 2014: 15 · 2013: 23 · 2012: 20
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- microglial activation, macrophage colony-stimulating factor, Iba1, Rac GTPase, phospholipase C-gamma, PI3K signaling, Fc receptors, actin cytoskeleton remodeling, intracellular signaling, calcium-binding proteins
- MeSH terms
- Animals, Calcium-Binding Proteins, DNA-Binding Proteins, Humans, Isoenzymes, Microfilament Proteins, Molecular Sequence Data, Phagocytosis, Type C Phospholipases, Signal Transduction, Macrophage Colony-Stimulating Factor, Receptor, Macrophage Colony-Stimulating Factor, Sequence Homology, Amino Acid, Microglia, Phosphatidylinositol 3-Kinases, rac GTP-Binding Proteins, Phospholipase C gamma
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