Structural Basis for Draxin-Modulated Axon Guidance and Fasciculation by Netrin-1 through DCC
Open accessAbstract
Axon guidance involves the spatiotemporal interplay between guidance cues and membrane-bound cell-surface receptors, present on the growth cone of the axon. Netrin-1 is a prototypical guidance cue that binds to deleted in colorectal cancer (DCC), and it has been proposed that the guidance cue Draxin modulates this interaction. Here, we present structural snapshots of Draxin/DCC and Draxin/Netrin-1 complexes, revealing a triangular relationship that affects Netrin-mediated haptotaxis and fasciculation. Draxin interacts with DCC through the N-terminal four immunoglobulin domains, and Netrin-1 through the EGF-3 domain, in the same region where DCC binds. Netrin-1 and DCC bind to adjacent sites on Draxin, which appears to capture Netrin-1 and tether it to the DCC receptor. We propose the conformational flexibility of the single-pass membrane receptor DCC is used to promote fasciculation and regulate axon guidance through concerted Netrin-1/Draxin binding. VIDEO ABSTRACT.
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DCC is a master regulator of axon guidance through interactions with netrin-1 and draxin.
“Prior studies showed that DCC is a master regulator of axon guidance (through its interactions with netrin-1 and draxin (Liu et al., 2018).”
From Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders (2019) · cites this paper as Liu et al., 2018
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- Authors
- Liu, Y., Bhowmick, T., Liu, Y., Gao, X., Mertens, H. D. T., Svergun, D. I., Xiao, J., Zhang, Y., Wang, J.-H., & Meijers, R.
- Affiliations
- Peking University (CN)
- European Molecular Biology Laboratory (DE)
- Harvard University (US)
- Corresponding author
- Xiao, Junyu
- Zhang, Yan
- Wang, Jia-huai
- Meijers, Rob
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 97
- Issue
- 6
- Pages
- 1261-1267.e4
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC5871715
- OpenAlex
- W2793037512
- Cited by
- 60
- References
- 46
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 5 · 2023: 3 · 2022: 9 · 2021: 8 · 2020: 10 · 2019: 9 · 2018: 2
- FWCI
- 3.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuron (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Desy Publications Database (Deutsches Elektronen-Synchrotron DESY) (submittedVersion, cc-by)
- Funders
- NIH (HL103526)
- Peking-Tsinghua Center for Life Sciences
- NSFC Major Research (31630028, 91632305)
- National Science Foundation of China (NSFC) Fund for Distinguished Young Scholars (81425009)
- National Science Foundation of China (31570735)
- National Key Research and Development Program of China (2017YFA0505200, 2016YFC0906000)
- 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 › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Draxin, netrin-1, DCC receptor, axon guidance, fasciculations, haptotaxis, immunoglobulin domains, conformational flexibility, growth cones
- MeSH terms
- Axon Guidance, Netrin-1, DCC Receptor, Amino Acid Sequence, Animals, Chlorocebus aethiops, Humans, Nerve Tissue Proteins, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, COS Cells, Intercellular Signaling Peptides and Proteins, HEK293 Cells
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