Structural Basis for Draxin-Modulated Axon Guidance and Fasciculation by Netrin-1 through DCC

Structural Basis for Draxin-Modulated Axon Guidance and Fasciculation by Netrin-1 through DCC

Axon guidance involves the spatiotemporal interplay between guidance cues and membrane-bound cell-surface receptors, present on the growth cone of the axon. Netrin-1 is a prototypical guidance cue that binds to deleted in colorectal cancer (DCC), and it has been proposed that the guidance cue Draxin modulates this interaction. Here, we present structural snapshots of Draxin/DCC and Draxin/Netri...

Draxin inhibits axonal outgrowth through the netrin receptor DCC.

Draxin, a recently identified axon guidance protein, is essential for the formation of forebrain commissures, and can mediate repulsion of netrin-stimulated spinal commissural axons. Here, we report that draxin binds multiple netrin receptors: DCC (deleted in colorectal cancer), Neogenin, UNC5s (H1, H2, H3), and DSCAM (Down's syndrome cell adhesion molecule). Since draxin and Dcc knockouts show...

DCC association with lipid rafts is required for netrin-1-mediated axon guidance.

During development, axons migrate long distances in responses to attractive or repulsive signals that are detected by their growth cones. One of these signals is mediated by netrin-1, a diffusible laminin-related molecule that both attracts and repels growth cones via interaction with its receptor DCC (deleted in colorectal cancer). Here we show that DCC in both commissural neurons and immortal...

Netrin-1/DCC signaling in commissural axon guidance requires cell-autonomous expression of heparan sulfate.

There is increasing evidence that heparan sulfate (HS) plays an essential role in various axon guidance processes. These observations, however, have not addressed whether HS is required cell autonomously as an axonal coreceptor or as an environmental factor that modulates the localization of guidance molecules in the terrain in which growing axons navigate. Here we demonstrate that netrin-1-med...

Draxin Inhibits Olfactory Bulb and Cortical Axonal Outgrowth through the Netrin Receptor Dcc