Netrin-1 is a highly conserved, pleiotropic signaling molecule that can serve as a neuronal chemorepellent during vertebrate development. In vertebrates, chemorepellent signaling is mediated through the tyrosine kinase, src-1, and the tyrosine phosphatase, shp-2. Tetrahymena thermophila has been used as a model system for chemorepellent signaling because its avoidance response is easily characterized under a light microscope. Our experiments showed that netrin-1 peptide is a chemorepellent in T. thermophila at micromolar concentrations. T. thermophila adapts to netrin-1 over a time course of about 10 minutes. Netrin-adapted cells still avoid GTP, PACAP-38, and nociceptin, suggesting that netrin does not use the same signaling machinery as any of these other repellents. Avoidance of netrin-1 peptide was effectively eliminated by the addition of the tyrosine kinase inhibitor, genistein, to the assay buffer; however, immunostaining using an anti-phosphotyrosine antibody showed similar fluorescence levels in control and netrin-1 exposed cells, suggesting that tyrosine phosphorylation is not required for signaling to occur. In addition, ELISA indicates that a netrin-like peptide is present in both whole cell extract and secreted protein obtained from Tetrahymena thermophila. Further study will be required in order to fully elucidate the signaling mechanism of netrin-1 peptide in this organism.
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http://dx.doi.org/10.1155/2016/7142868 | DOI Listing |
Nat Commun
January 2025
Neuronal Cell Biology Division, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38104, USA.
Exiting a germinal zone (GZ) initiates a cascade of events that promote neuronal maturation and circuit assembly. Developing neurons and their progenitors must interpret various niche signals-such as morphogens, guidance molecules, extracellular matrix components, and adhesive cues-to navigate this region. How differentiating neurons in mouse brains integrate and adapt to multiple cell-extrinsic niche cues with their cell-intrinsic machinery in exiting a GZ is unknown.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
Department of Neurosurgery, the Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518000, China; Neurobiology Research Center, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen 518000, China. Electronic address:
Currently, stroke is a disease with high disability and mortality risks and no effective treatment. The pathogenesis and molecular mechanisms of neuronal damage in stroke are highly complex. Pyroptosis participates in neuronal death after stroke.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Paris Cardiovascular Research Center, Université Paris Cité, Inserm U970, Paris F-75015, France.
The integrity of the blood-retina barrier (BRB) is crucial for phototransduction and vision, by tightly restricting transport of molecules between the blood and surrounding neuronal cells. Breakdown of the BRB leads to the development of retinal diseases. Here, we show that Netrin-1/Unc5b and Norrin/Lrp5 signaling establish a zonated endothelial cell gene expression program that controls BRB integrity.
View Article and Find Full Text PDFCell Rep
November 2024
Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Intellectual & Developmental Disabilities Research Center, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:
We have identified an unexpected role for netrin1, a canonical axonal guidance cue, as a suppressor of bone morphogenetic protein (Bmp) signaling in the developing dorsal spinal cord. Using a combination of gain- and loss-of-function approaches in chicken and mouse embryonic models, as well as mouse embryonic stem cells (mESCs), we have observed that manipulating the level of netrin1 specifically alters the patterning of the Bmp-dependent dorsal interneurons (dIs), dI1-dI3. Altered netrin1 levels also change Bmp signaling activity, as assessed using bioinformatic approaches, as well as monitoring phosophoSmad1/5/8 activation, the canonical intermediate of Bmp signaling, and Id levels, a known Bmp target.
View Article and Find Full Text PDFBiochem Biophys Res Commun
December 2024
Laboratory of Stress Medicine, Faculty of Psychology, Navy Medical University, 800 Xiangyin Road, Shanghai, 200433, China. Electronic address:
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