Semaphorin 3A displays a punctate distribution on the surface of neuronal cells and interacts with proteoglycans in the extracellular matrix
Abstract
Secreted semaphorins are essential for neural development and continue to be expressed in subpopulations of adult neurons, where they subserve as yet unknown functions. We employed functional myc- and GFP-tagged Sema3A proteins to obtain insight in the localization of Sema3A in neuronal cells. Sema3A localized to both axons and dendrites of cortical neurons. GFP-Sema3A exhibited a characteristic punctate distribution on the surface of Neuro-2a cells, localized to migratory pathways of cultured cells, and co-localized with and induced clustering of its receptor component neuropilin-1. Treatment with excess glycosaminoglycans and chondroitinase ABC resulted in the removal of cell surface Sema3A. Heparin enhanced Sema3A's binding to neuropilin-1-expressing cells and potentiated its growth cone collapsing activity. Together, these results indicate that association with proteoglycans in the extracellular matrix of neuronal cells plays an important role in the localization of the chemorepulsive guidance cue Sema3A, and that this interaction may enhance its biological activity.
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CSPGs, especially their GAG moieties, may inhibit growth by presenting growth-inhibitory proteins.
“Specifically, CSPGs, and particularly their GAG moieties, may act by i) binding to a specific receptor; ii) blocking the growth-promoting activity of integrins; iii) presenting growth-inhibitory proteins.”
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 De Wit et al., 2005
Another potential mechanism of PNN action may rely on binding of GAG chains to ligands with growth-inhibitory or repulsive effects.
“Another potential mechanism of action of PNNs may rely on the binding of GAG chains to ligands harboring growth-inhibitory or repulsive effects.”
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 De Wit et al., 2005
Sema3A is a PNN component.
“Recently, the repulsive guidance molecule semaphorin3A (Sema3A) has been identified as a PNN component (De Wit et al., 2005;Vo et al., 2013).”
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 De Wit et al., 2005
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- Authors
- De Wit, J., De Winter, F., Klooster, J., & Verhaagen, J.
- Corresponding author
- Verhaagen, Joost
- ORCID
- Verhaagen, Joost
- Venue
- Molecular and Cellular Neuroscience
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 29
- Issue
- 1
- Pages
- 40-55
- ISSN
- 1044-7431 (ISSN-L)
- OpenAlex
- W2078936926
- Cited by
- 154
- References
- 92
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 7 · 2023: 7 · 2022: 5 · 2021: 9 · 2020: 6 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 9 · 2015: 11 · 2014: 9 · 2013: 14 · 2012: 8
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Lirias (KU Leuven) (submittedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Keywords
- semaphorin 3A, neuropilin-1, proteoglycans, extracellular matrix, glycosaminoglycans, chondroitinase ABC, cell surface localization, growth cone collapse, axons and dendrites, cortical neurons, N2a cells, heparin binding
- MeSH terms
- Animals, Anticoagulants, Epitopes, Cerebral Cortex, Heparin, Membrane Proteins, Neuroblastoma, Neurons, Protein Binding, Proteoglycans, Tumor Cells, Cultured, Proto-Oncogene Proteins c-myc, Extracellular Matrix Proteins, Rats, Wistar, Growth Cones, Neuropilin-1, Semaphorin-3A, Green Fluorescent Proteins, Mice, Rats
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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