Sialic acid on the neuronal glycocalyx prevents complement C1 binding and complement receptor-3-mediated removal by microglia
Open accessAbstract
Microglial cells are professional phagocytes of the CNS responsible for clearance of unwanted structures. Neuronal processes are marked by complement C1 before they are removed in development or during disease processes. Target molecules involved in C1 binding and mechanisms of clearance are still unclear. Here we show that the terminal sugar residue sialic acid of the mouse neuronal glycocalyx determines complement C1 binding and microglial-mediated clearance function. Several early components of the classical complement cascade including C1q, C1r, C1s, and C3 were produced by cultured mouse microglia. The opsonin C1q was binding to neurites after enzymatic removal of sialic acid residues from the neuronal glycocalyx. Desialylated neurites, but not neurites with intact sialic acid caps, were cleared and taken up by cocultured microglial cells. The removal of the desialylated neurites was mediated via the complement receptor-3 (CR3; CD11b/CD18). Data demonstrate that mouse microglial cells via CR3 recognize and remove neuronal structures with an altered neuronal glycocalyx lacking terminal sialic acid.
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The complement participates in the physiological process termed synaptic pruning; synapses and axons have to be labeled by complement components C1q and C3 before being phagocytosed, which prompts their selective recognition by microglial cells.
“The complement also participates in the physiological process, termed synaptic pruning. The synapses and axons have to be labeled by complement components C1q and C3 before being phagocytosed, which prompts their selective recognition by microglial cells (Paolicelli et al., 2011; Linnartz et al., 2012; Schafer et al., 2012).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Linnartz et al., 2012
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- Authors
- Linnartz, B., Kopatz, J., Tenner, A. J., & Neumann, H.
- Affiliations
- University of Bonn (DE)
- University of California, Irvine (US)
- University Hospital Bonn (DE)
- Corresponding author
- Neumann, Harald
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-01-18
- Volume
- 32
- Issue
- 3
- Pages
- 946-952
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4037907
- OpenAlex
- W2167842125
- Cited by
- 134
- References
- 28
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 10 · 2023: 7 · 2022: 10 · 2021: 18 · 2020: 12 · 2019: 6 · 2018: 6 · 2017: 10 · 2016: 4 · 2015: 11 · 2014: 13 · 2013: 8 · 2012: 7
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (KFO177, SFB 704, FOR1336)
- National Institutes of Health (SFB704, AG00538)
- University of California, Irvine
- National Institute on Aging (P01AG000538, AG 00538)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- sialic acid, complement C1, C1q, complement receptor 3, CD11b/CD18, microglial phagocytosis, desialylation, classical complement pathway, C1r, C1s, complement C3
- MeSH terms
- Analysis of Variance, Animals, Animals, Newborn, Brain, Cells, Cultured, Complement C3, Embryo, Mammalian, Female, Flow Cytometry, Gene Expression Regulation, Humans, Lipopolysaccharides, Male, Mice, Inbred C57BL, Neuraminidase, Neurons, Protein Binding, Receptors, Complement, Sialic Acids, Transfection, Tubulin, Antigens, CD, Complement C1q, Cytokines, Microglia, Coculture Techniques, Glycocalyx, CD11b Antigen, Green Fluorescent Proteins, Mice
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