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

Gao, X., Metzger, U., Panza, P., Mahalwar, P., Alsheimer, S., Geiger, H., et al. (2015). A Floor-Plate Extracellular Protein-Protein Interaction Screen Identifies Draxin as a Secreted Netrin-1 Antagonist. Cell Reports, 12(4), 694-708. doi:10.1016/j.celrep.2015.06.047.

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 Creators:
Gao, X1, Author           
Metzger, U, Author
Panza, P1, Author                 
Mahalwar, P1, Author           
Alsheimer, S1, Author           
Geiger, H1, Author           
Maischein, H-M1, Author           
Levesque, MP1, Author           
Templin, M, Author
Söllner, C1, Author           
Affiliations:
1Department Genetics, Max Planck Institute for Developmental Biology, Max Planck Society, ou_3375716              

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 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.

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 Dates: 2015-07
 Publication Status: Issued
 Pages: -
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 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.celrep.2015.06.047
PMID: 26190107
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Title: Cell Reports
Source Genre: Journal
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Publ. Info: Maryland Heights, MO : Cell Press
Pages: - Volume / Issue: 12 (4) Sequence Number: - Start / End Page: 694 - 708 Identifier: ISSN: 2211-1247
CoNE: https://pure.mpg.de/cone/journals/resource/2211-1247