Versican V1 Isoform Induces Neuronal Differentiation and Promotes Neurite Outgrowth
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The chondroitin sulfate proteoglycan versican is one of the major extracellular components in the developing and adult brain. Here, we show that isoforms of versican play different roles in neuronal differentiation and neurite outgrowth. Expression of versican V1 isoform in PC12 cells induced complete differentiation, whereas expression of V2 induced an aborted differentiation accompanied by apoptosis. V1 promoted neurite outgrowth of hippocampal neurons, but V2 failed to do so. V1 transfection enhanced expression of epidermal growth factor receptor and integrins, and facilitated sustained extracellular signal-regulated kinase/MAPK phosphorylation. Blockade of the epidermal growth factor receptor, β1 integrin, or Src significantly inhibited neuronal differentiation. Finally, we demonstrated that versican V1 isoform also promoted differentiation of neural stem cells into neurons. Our results have implications for understanding how versican regulates neuronal development, function, and repair.
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VCAN carries three HHMCs.
“Versican (VCAN), which promotes neurite outgrowth98, carries three HHMCs”
From A catalog of single nucleotide changes distinguishing modern humans from archaic hominins (2019) · cites this paper as [98]
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“CSPGs, and versican in particular, promote axon outgrowth (Wu et al., 2004; Maeda, 2010; Klausmeyer et al., 2011).”
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- Authors
- Wu, Y., Sheng, W., Chen, L., Dong, H., Lee, V., Lu, F., Wong, C. S., Lu, W.-Y., & Yang, B. B.
- Affiliations
- Sunnybrook Health Science Centre (CA)
- Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada
- Venue
- Molecular Biology of the Cell
- Published
- 2004-05
- Volume
- 15
- Issue
- 5
- Pages
- 2093-2104
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC404007
- OpenAlex
- W2146306557
- Cited by
- 107
- References
- 50
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 9 · 2020: 5 · 2019: 4 · 2018: 8 · 2017: 3 · 2016: 3 · 2015: 7 · 2014: 7 · 2013: 2 · 2012: 6
- FWCI
- 3.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Biology of the Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- neuronal differentiation, neurite outgrowth, chondroitin sulfate proteoglycans, PC12 cells, hippocampal neurons, epidermal growth factor receptor, beta1 integrin, Src kinase, ERK signaling, neural stem cell differentiation, apoptosis, neuronal development, brain extracellular matrix
- MeSH terms
- Animals, Carrier Proteins, Cell Differentiation, Genetic Vectors, Glycoproteins, Hippocampus, Nerve Growth Factors, Nerve Tissue Proteins, Neurons, Phosphorylation, Quinones, Transfection, Gene Expression, Integrins, Cyclins, Benzoquinones, Neurites, PC12 Cells, Rifabutin, Integrin beta1, Protein Isoforms, Mitogen-Activated Protein Kinase Kinases, Lactams, Macrocyclic, Rats, Versicans, ErbB Receptors
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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