title: A Floor-Plate Extracellular Protein-Protein Interaction Screen Identifies Draxin as a Secreted Netrin-1 Antagonist.
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.
authors.affiliation: Max Planck Institute for Developmental Biology, Genetics, Spemannstraße 35, 72076 Tübingen, Germany. Electronic address: xuefan.gao@tuebingen.mpg.de.
authors.forename: Xuefan
authors.initials: X
authors.lastname: Gao
authors.affiliation: Natural and Medical Sciences Institute at the University of Tübingen, Markwiesenstraße 55, 72770 Reutlingen, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Metzger
authors.affiliation: Max Planck Institute for Developmental Biology, Genetics, Spemannstraße 35, 72076 Tübingen, Germany.
authors.forename: Paolo
authors.initials: P
authors.lastname: Panza
authors.affiliation: Max Planck Institute for Developmental Biology, Genetics, Spemannstraße 35, 72076 Tübingen, Germany.
authors.forename: Prateek
authors.initials: P
authors.lastname: Mahalwar
authors.affiliation: Max Planck Institute for Developmental Biology, Genetics, Spemannstraße 35, 72076 Tübingen, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Alsheimer
authors.affiliation: Max Planck Institute for Developmental Biology, Genetics, Spemannstraße 35, 72076 Tübingen, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Geiger
authors.affiliation: Max Planck Institute for Developmental Biology, Genetics, Spemannstraße 35, 72076 Tübingen, Germany.
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Maischein
authors.affiliation: Max Planck Institute for Developmental Biology, Genetics, Spemannstraße 35, 72076 Tübingen, Germany.
authors.forename: Mitchell P
authors.initials: MP
authors.lastname: Levesque
authors.affiliation: Natural and Medical Sciences Institute at the University of Tübingen, Markwiesenstraße 55, 72770 Reutlingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Templin
authors.affiliation: Max Planck Institute for Developmental Biology, Genetics, Spemannstraße 35, 72076 Tübingen, Germany. Electronic address: christian-soellner@outlook.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Söllner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D000075388:Netrin-1; D011485:Protein Binding; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D025521:Tumor Suppressor Proteins; D029961:Zebrafish Proteins; C573155:draxin protein, zebrafish; D000075388:Netrin-1