In vitro modeling of perineuronal nets: hyaluronan synthase and link protein are necessary for their formation and integrity
Abstract
J. Neurochem. (2010) 114 , 1447–1459. We have previously shown that all perineuronal nets (PNNs) bearing neurons express a hyaluronan synthase (HAS), a link protein (usually cartilage link protein‐1; Crtl1) and a chondroitin sulfate proteoglycan (usually aggrecan). Animal lacking Crtl1 in the CNS lacks normal PNNs. PNNs are implicated in the control of neuronal plasticity, and interventions to modulate PNN formation will be useful for manipulating plasticity. We have developed an in vitro model which demonstrates how the structural components of PNNs trigger their formation, using human embryonic kidney cells, which do not normally produce a pericellular matrix. Expression of HAS3 leads to the production of a diffuse matrix. It was converted into a compact PNN‐like structure when the cells also expressed Crtl1 and aggrecan. This matrix was stained by Wisteria floribunda , contained Crtl1 and aggrecan, and like PNNs, could only be solubilized in 6 M urea. In the absence of hyaluronan produced by HAS3, aggrecan and Crtl1 dissipated into the medium, but when the cells were transfected to produce a hyaluronan matrix, Crtl1 and aggrecan were incorporated into it. Cells lacking any one of these molecules showed impaired integrity of the PNNs. Cells expressing HAS3 and Crtl1 were able to incorporate exogenous aggrecan into their pericellular matrix.
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Hyaluronan is synthesized by hyaluronan synthase (HAS), which anchors nascent hyaluronan chains to the neuronal surface together with ankyrin-R and RPTPzeta/phosphacan.
“Hyaluronan is synthesized by the transmembrane enzyme hyaluronan synthase (HAS), which anchors the nascent hyaluronan chains to the neuronal surface [15] together with ankyrin-R [16] and RPTPzeta/phosphacan [17].”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [15]
Long hyaluronan chains provide a scaffold for the assembly of CSPGs, hyaluronan, hyaluronin and proteoglycan link proteins (Hapln), and tenascins.
“The long hyaluronan chains provide a scaffold for the assembly of CSPGs, hyaluronan, hyaluronin and proteoglycan link proteins (Hapln), and tenascins [15, 18].”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [15]
In the HEK model, overexpression of Hapln1/Crtl1 in HAS-3 expressing cells results in formation of a compact pericellular matrix.
“For example, in the HEK model, the overexpression of Hapln1/Crtl1 in HAS-3 expressing cells, which form a diffuse pericellular matrix, results in the formation of a compact pericellular matrix (Kwok et al., 2010).”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Kwok et al., 2010
Aggrecan is necessary for perineuronal net formation.
“Notably, aggrecan is necessary for PNN formation, as shown in the HEK cell model (Kwok et al., 2010) and in organotypic cultures derived from aggrecan knockout mice (Giamanco et al., 2010).”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Kwok et al., 2010
Transfection of the HAS-3 gene in human embryonic kidney cells is sufficient for formation of a PNN-like matrix on the cell surface.
“Indeed, transfection of HAS-3 gene in human embryonic kidney (HEK) cells is sufficient for the formation of a PNN-like matrix on the cell surface (Kwok et al., 2010).”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Kwok et al., 2010
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- Authors
- Kwok, J. C. F., Carulli, D., & Fawcett, J. W.
- Affiliations
- University of Cambridge (GB)
- University of Turin (IT)
- Corresponding author
- Fawcett, James W.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2010-08-02
- Volume
- 114
- Issue
- 5
- Pages
- 1447-1459
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1501527294
- Cited by
- 170
- References
- 7
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 13 · 2023: 12 · 2022: 9 · 2021: 10 · 2020: 14 · 2019: 16 · 2018: 11 · 2017: 13 · 2016: 8 · 2015: 12 · 2014: 7 · 2013: 10 · 2012: 6
- FWCI
- 3.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Dana Foundation
- Christopher and Dana Reeve Foundation
- European Commission
- Fondation pour la Recherche Médicale
- John and Lucille Van Geest Foundation
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- perineuronal nets, hyaluronan synthase, HAS3, aggrecan, chondroitin sulfate proteoglycans, pericellular matrix, in vitro model, neuroplasticity, urea solubility
- MeSH terms
- Hyaluronan Synthases, Proteoglycan Link Protein, Cell Line, Humans, Nerve Net, Neuronal Plasticity, Oligodendroglia, Proteoglycans, Glucuronosyltransferase, Extracellular Matrix Proteins
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