Draxin inhibits axonal outgrowth through the netrin receptor DCC

Ahmed, Giasuddin; Shinmyo, Yohei; Ohta, Kunimasa; Islam, Shahidul; Hossain, Mahmud; Naser, Iftekhar Bin; Riyadh, Asrafuzzaman; Su, Yuhong; Zhang, Sanbing; Tessier‐Lavigne, Marc; Tanaka, Hideaki

doi:10.1016/j.neures.2011.07.286

Cited by 22 publications

(35 citation statements)

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“…This hypothesis differs from a previously proposed model (Ahmed et al, 2011) in which Draxin serves as an inhibitory ligand for the Netrin receptor DCC. To test whether Draxin has an influence on Netrin's ability to bind Netrin receptors, we developed a competition assay based on AVEXIS ( Figure 4A).…”

Section: Draxin Competes With Netrin Receptors For Netrin Bindingcontrasting

confidence: 98%

“…More importantly, we did not observe physical interactions between all tested pairs of zebrafish or human Draxin and Netrin receptors. These findings disagree with an earlier report (Ahmed et al, 2011) but agree with a recent study, which failed to detect a direct interaction between human Draxin and DCC using Surface Plasmon Resonance (SPR) (Haddick et al, 2014).…”

Section: Draxin Selectively Binds To G-netrinscontrasting

confidence: 78%

“…In our screen, we detected a direct interaction between Draxin and Netrin-1. Draxin has been previously suggested to be a functional important component of the Netrin signaling pathway, by directly engaging Netrin receptors (Ahmed et al, 2011;Chen et al, 2013). It has been reported that Draxin, unlike Netrin-1, is involved in repulsive axon responses upon binding to DCC.…”

Section: Discussionmentioning

confidence: 99%

“…The phenotypic similarities suggest that both secreted factors might act in the same signaling cascade. In addition, it has been reported (Ahmed et al, 2011) that Draxin binds to a structurally diverse set of Netrin receptors (DCC/Neo1, Unc5, Dscam).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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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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Section: Draxin Competes With Netrin Receptors For Netrin Bindingcontrasting

confidence: 98%

Section: Draxin Selectively Binds To G-netrinscontrasting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2015

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“…DRAXIN, dorsal repulsive axon guidance protein, is an axon guidance protein expressed in many brain regions during development. It is essential for the formation of forebrain commissures and can mediate repulsion of netrin-stimulated spinal commissural axons (Ahmed et al, 2011). FCER2, the human leukocyte differentiation antigen CD23, is a key molecule for B-cell activation and growth.…”

Section: Tablementioning

confidence: 99%

Identification of candidate genes for Parkinson's disease through blood transcriptome analysis in LRRK2-G2019S carriers, idiopathic cases, and controls

Infante

Prieto

Sierra

et al. 2015

Neurobiology of Aging

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Emerging data on the use of anti‐tumor necrosis factor‐alpha medications in pregnancy

Chambers

Johnson

2012

Birth Defects Research

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Anti-tumor necrosis factor (TNF) α medications are used for the treatment of a number of autoimmune diseases. Evaluation of pregnancy safety for these medications is complicated by the contribution of the underlying maternal disease to adverse pregnancy outcomes, such as preterm delivery and reduced birth weight. Placental transport of these medications is thought to be minimal in the first trimester, thereby providing some reassurance regarding theoretical risks for congenital malformations. Available human exposure data are sparse; however, to date there has been no convincing evidence to support an increased risk for a specific pattern of major congenital malformations with any of the drugs in this group for which some data is currently available. As a result of the improvement of symptoms during pregnancy in some women with autoimmune diseases, it may be possible to discontinue treatment before or shortly after conception. However, in some cases the benefits of treatment and concerns for disease flares in pregnancy have warranted continued treatment during pregnancy. Because of the relatively long half-life of these medications, and theoretical concerns for immune compromise of the infant following exposure in the latter two trimesters, some clinicians recommend discontinuation of treatment in the third trimester to avoid potentially prolonged infant exposure in the postpartum period. Currently ongoing controlled cohort studies for some of the TNF blocker medications will help to provide more definitive answers for clinicians and patients.

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Draxin inhibits axonal outgrowth through the netrin receptor DCC

Cited by 22 publications

References 0 publications

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

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

Identification of candidate genes for Parkinson's disease through blood transcriptome analysis in LRRK2-G2019S carriers, idiopathic cases, and controls

Emerging data on the use of anti‐tumor necrosis factor‐alpha medications in pregnancy

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