ArticlePLoS genetics2015
Slit-Dependent Endocytic Trafficking of the Robo Receptor Is Required for Son of Sevenless Recruitment and Midline Axon Repulsion.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- The Slit-Robo signalling pathway in nervous system development: a comparative perspective from vertebrates and invertebrates.Open biology · 2025Review
- Article
- Glu592 of the axon guidance receptor ROBO3 mediates a pH-dependent interaction with NELL2 ligand.FEBS letters · 2025Article
- A human DCC variant causing mirror movement disorder reveals that the WAVE regulatory complex mediates axon guidance by netrin-1-DCC.Science signaling · 2024Article
- Article
- HTT (huntingtin) and RAB7 co-migrate retrogradely on a signaling LAMP1-containing late endosome during axonal injury.Autophagy · 2023Article
- Intracellular Trafficking Mechanisms that Regulate Repulsive Axon Guidance.Neuroscience · 2023Review
- Tace/ADAM17 is a bi-directional regulator of axon guidance that coordinates distinct Frazzled and Dcc receptor signaling outputs.Cell reports · 2022Article
- CD36International journal of molecular sciences · 2022Article
- Slit-Robo signalling establishes a Sphingosine-1-phosphate gradient to polarise fin mesenchyme.EMBO reports · 2022Article
- Autocrine/Paracrine Slit-Robo Signaling Controls Optic Lobe Development inFrontiers in cell and developmental biology · 2022Article
- Robo recruitment of the Wave regulatory complex plays an essential and conserved role in midline repulsion.eLife · 2021Article
- Conserved and divergent aspects of Robo receptor signaling and regulation between Drosophila Robo1 and C. elegans SAX-3.Genetics · 2021Article
- New insights into the molecular mechanisms of axon guidance receptor regulation and signaling.Current topics in developmental biology · 2021Review
- Molecular mechanisms regulating axon responsiveness at the midline.Developmental biology · 2020Article
- Critical Decrease in the Level of Axon Guidance Receptor ROBO1 in Rod Synaptic Terminals Is Followed by Axon Retraction.Investigative ophthalmology & visual science · 2020Article
- Minimal structural elements required for midline repulsive signaling and regulation of Drosophila Robo1.PloS one · 2020Article
- Commissural axon guidance in the developing spinal cord: from Cajal to the present day.Neural development · 2019Review
- Endophilin-A2 dependent VEGFR2 endocytosis promotes sprouting angiogenesis.Nature communications · 2019Article
- A crucial role for Arf6 in the response of commissural axons to Slit.Development (Cambridge, England) · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Understanding how axon guidance receptors are activated by their extracellular ligands to regulate growth cone motility is critical to learning how proper wiring is established during development. Roundabout (Robo) is one such guidance receptor that mediates repulsion from its ligand Slit in both invertebrates and vertebrates. Here we show that endocytic trafficking of the Robo receptor in response to Slit-binding is necessary for its repulsive signaling output. Dose-dependent genetic interactions and in vitro Robo activation assays support a role for Clathrin-dependent endocytosis, and entry into both the early and late endosomes as positive regulators of Slit-Robo signaling. We identify two conserved motifs in Robo's cytoplasmic domain that are required for its Clathrin-dependent endocytosis and activation in vitro; gain of function and genetic rescue experiments provide strong evidence that these trafficking events are required for Robo repulsive guidance activity in vivo. Our data support a model in which Robo's ligand-dependent internalization from the cell surface to the late endosome is essential for receptor activation and proper repulsive guidance at the midline by allowing recruitment of the downstream effector Son of Sevenless in a spatially constrained endocytic trafficking compartment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.