ArticleNature cell biology2008
Netrin-1 mediates neuronal survival through PIKE-L interaction with the dependence receptor UNC5B.
Article in Nature cell biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 98 citations in OpenAlex.
- Neuronal guidance signaling in neurodegenerative diseases: Key regulators that function at neuron-glia and neuroimmune interfaces.Neural regeneration research · 2026Article
- NTN-1 attenuates amyloid-β-mediated microglial neuroinflammation and memory impairment via the NF-κB pathway and NLRP3 inflammasome in a rat model of Alzheimer's disease.Frontiers in aging neuroscience · 2025Article
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- IER3IP1-mutations cause microcephaly by selective inhibition of ER-Golgi transport.Cellular and molecular life sciences : CMLS · 2024Article
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- Insights from the neural guidance factor Netrin-1 into neurodegeneration and other diseases.Frontiers in molecular neuroscience · 2024Review
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- The couple of netrin-1/α-Synuclein regulates the survival of dopaminergic neurons via α-Synuclein disaggregation.BMB reports · 2023Article
- Fibronectin leucine-rich transmembrane protein 2 drives monocyte differentiation into macrophagesFrontiers in immunology · 2023Article
- Interactions between genes involved in physiological dysregulation and axon guidance: role in Alzheimer's disease.Frontiers in genetics · 2023Article
- UNC5C Receptor Proteolytic Cleavage by Active AEP Promotes Dopaminergic Neuronal Degeneration in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Transcriptomics-Based Phenotypic Screening Supports Drug Discovery in Human Glioblastoma Cells.Cancers · 2021Article
- Netrin-1 receptor UNC5C cleavage by active δ-secretase enhances neurodegeneration, promoting Alzheimer's disease pathologies.Science advances · 2021Article
- Netrin-1 and its receptor DCC modulate survival and death of dopamine neurons and Parkinson's disease features.The EMBO journal · 2021Article
- UNC5B mediates G2/M phase arrest of bladder cancer cells by binding to CDC14A and P53.Cancer gene therapy · 2020Article
- Netrin1 deficiency activates MST1 via UNC5B receptor, promoting dopaminergic apoptosis in Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Polyomavirus Small T Antigen Induces Apoptosis in Mammalian Cells through the UNC5B Pathway in a PP2A-Dependent Manner.Journal of virology · 2020Article
- Lack of Myosin X Enhances Osteoclastogenesis and Increases Cell Surface Unc5b in Osteoclast-Lineage Cells.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Article
- Cellular energy stress induces AMPK-mediated regulation of glioblastoma cell proliferation by PIKE-A phosphorylation.Cell death & disease · 2019Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Netrins, a family of secreted molecules, have critical functions in axon guidance and cell migration during neuronal development. In addition to its role as a chemotropic molecule, netrin-1 also acts as a survival factor. Both UNC5 (that is, UNC5A, UNC5B, UNC5C or UNC5D) and DCC are transmembrane receptors for netrin-1 (Refs 8, 9). In the absence of netrin-1, DCC and UNC5 act as dependence receptors and trigger apoptosis. However, how netrin-1 suppresses the apoptotic activity of the receptors remains elusive. Here we show that netrin-1 induces interaction of UNC5B with the brain-specific GTPase PIKE-L. This interaction triggers the activation of PtdIns-3-OH kinase signalling, prevents UNC5B's pro-apoptotic activity and enhances neuronal survival. Moreover, this process relies strongly on Fyn because PIKE-L is tyrosine phosphorylated in response to netrin-1, and the netrin-1-mediated interaction of UNC5B with PIKE-L is inhibited in Fyn-null mice. Thus, PIKE-L acts as a downstream survival effector for netrin-1 through UNC5B in the nervous system.
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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.