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Cell Rep. 2015 Jul 28;12(4):694-708. doi: 10.1016/j.celrep.2015.06.047. Epub 2015 Jul 16.

A Floor-Plate Extracellular Protein-Protein Interaction Screen Identifies Draxin as a Secreted Netrin-1 Antagonist.

Author information

1
Max Planck Institute for Developmental Biology, Genetics, Spemannstraße 35, 72076 Tübingen, Germany. Electronic address: xuefan.gao@tuebingen.mpg.de.
2
Natural and Medical Sciences Institute at the University of Tübingen, Markwiesenstraße 55, 72770 Reutlingen, Germany.
3
Max Planck Institute for Developmental Biology, Genetics, Spemannstraße 35, 72076 Tübingen, Germany.
4
Max Planck Institute for Developmental Biology, Genetics, Spemannstraße 35, 72076 Tübingen, Germany. Electronic address: christian-soellner@outlook.de.

Abstract

Floor-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.

PMID:
26190107
DOI:
10.1016/j.celrep.2015.06.047
[Indexed for MEDLINE]
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