Cited by 601Axon Guidance and Neuronal SignalingDevelopmental Biology and Gene RegulationNeurogenesis and neuroplasticity mechanisms

RETRACTED: Hierarchical Organization of Guidance Receptors: Silencing of Netrin Attraction by Slit Through a Robo/DCC Receptor Complex

Open access
Stein, Elke, Tessier-Lavigne, Marc·2001·Science

Abstract

Axonal growth cones that cross the nervous system midline change their responsiveness to midline guidance cues: They become repelled by the repellent Slit and simultaneously lose responsiveness to the attractant netrin. These mutually reinforcing changes help to expel growth cones from the midline by making a once-attractive environment appear repulsive. Here, we provide evidence that these two changes are causally linked: In the growth cones of embryonic Xenopus spinal axons, activation of the Slit receptor Roundabout (Robo) silences the attractive effect of netrin-1, but not its growth-stimulatory effect, through direct binding of the cytoplasmic domain of Robo to that of the netrin receptor DCC. Biologically, this hierarchical silencing mechanism helps to prevent a tug-of-war between attractive and repulsive signals in the growth cone that might cause confusion. Molecularly, silencing is enabled by a modular and interlocking design of the cytoplasmic domains of these potentially antagonistic receptors that predetermines the outcome of their simultaneous activation.

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Crossref · 10.1126/science.1058445This paper is marked retracted.

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30 of 30 references verified0 citation errors · 0 not checkable

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  • ROBO silences the attractive effect that Netrin 1 has on DCC, allowing SLIT2 to bind to this ligand and enabling axon pathfinding in the developing brain.

    “ROBO silences the attractive effect that Netrin 1 has on DCC, allowing SLIT2 to bind to this ligand and enabling axon pathfinding in the developing brain [106, 107].”

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2 retracted

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Authors
Stein, E., & Tessier-Lavigne, M.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Department of Anatomy and Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.
Venue
Science
Published
2001-03-09
Volume
291
Issue
5510
Pages
1928-1938
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W1964817578
Cited by
601
References
30
Citations by year
2025: 1 · 2024: 1 · 2023: 7 · 2022: 9 · 2021: 7 · 2020: 9 · 2019: 12 · 2018: 14 · 2017: 16 · 2016: 16 · 2015: 16 · 2014: 26 · 2013: 25 · 2012: 31
FWCI
20.57
Type
journal article
Language
en
Status
Retracted
Open access
Licence
cc-by
Locations
  • Science (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
axon guidance, netrin-1, slits, Roundabout receptors, DCC receptor, growth cones, midline crossing, receptor complex, cytoplasmic domain
MeSH terms
Netrin Receptors, Netrin-1, Roundabout Proteins, Slit Homolog 2 Protein, Animals, Axons, Cell Movement, Cells, Cultured, Cytoplasm, Embryo, Nonmammalian, Ligands, Mutation, Nerve Growth Factors, Nerve Tissue Proteins, Precipitin Tests, Receptors, Cell Surface, Receptors, Immunologic, Recombinant Fusion Proteins, Transfection, Xenopus, Signal Transduction, Cell Adhesion Molecules, Hepatocyte Growth Factor, Protein Structure, Tertiary, Growth Cones, Tumor Suppressor Proteins, Intercellular Signaling Peptides and Proteins

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