A Floor-Plate Extracellular Protein-Protein Interaction Screen Identifies Draxin as a Secreted Netrin-1 Antagonist
| Autor: | Paolo Panza, Ute Metzger, Markus F. Templin, Hans-Martin Maischein, Sören Alsheimer, Christian Söllner, Gao Xuefan, Horst Geiger, Mitchell P. Levesque, Prateek Mahalwar |
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| Rok vydání: | 2014 |
| Předmět: |
Cell signaling
animal structures Molecular Sequence Data Nerve Tissue Proteins Biology General Biochemistry Genetics and Molecular Biology Protein–protein interaction 03 medical and health sciences 0302 clinical medicine Netrin Extracellular Animals Amino Acid Sequence Nerve Growth Factors Receptor lcsh:QH301-705.5 Zebrafish 030304 developmental biology Floor plate 0303 health sciences Binding Sites Tumor Suppressor Proteins fungi Netrin-1 Zebrafish Proteins biology.organism_classification Cell biology lcsh:Biology (General) nervous system embryonic structures Axon guidance 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Cell Reports, Vol 12, Iss 4, Pp 694-708 (2015) |
| ISSN: | 2211-1247 |
| Popis: | SummaryFloor-plate-derived extracellular signaling molecules, including canonical axon guidance cues of the Netrin family, control neuronal circuit organization. Despite the importance of the floor plate as an essential signaling center in the developing vertebrate central nervous system, no systematic approach to identify binding partners for floor-plate-expressed cell-surface and secreted proteins has been carried out. Here, we used a high-throughput assay to discover extracellular protein-protein interactions, which likely take place in the zebrafish floor-plate microenvironment. The assembled floor-plate network contains 47 interactions including the hitherto-not-reported interaction between Netrin-1 and Draxin. We further characterized this interaction, narrowed down the binding interface, and demonstrated that Draxin competes with Netrin receptors for binding to Netrin-1. Our results suggest that Draxin functions as an extracellular Netrin signaling modulator in vertebrates. A reciprocal gradient of Draxin might shape or sharpen the active Netrin gradient, thereby critically modulating its effect. |
| Databáze: | OpenAIRE |
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