A Signaling Mechanism Coupling Netrin-1/Deleted in Colorectal Cancer Chemoattraction to SNARE-Mediated Exocytosis in Axonal Growth Cones

The Journal of Neuroscience, 2011 · DOI: 10.1523/JNEUROSCI.3018-11.2011 · Published: October 12, 2011

Simple Explanation

This research explains how Netrin-1, a guidance cue, uses a specific receptor (DCC) to control the growth and direction of nerve cells. The DCC receptor interacts with Syntaxin-1 (Sytx1), a protein important for membrane fusion, facilitating the growth cone's response to Netrin-1. The study reveals a new signaling mechanism linking Netrin-1/DCC, guiding nerve cells, and Sytx1/TI-VAMP, regulating membrane turnover for cell growth.

Study Duration

Not specified

Participants

Mouse and chicken neuronal cultures

Evidence Level

Level 3, In vitro and in vivo experiments

Key Findings

1
The Netrin-1 receptor DCC forms a protein complex with the t-SNARE protein Syntaxin-1 (Sytx1) in a Netrin-1-dependent manner.
2
Blockade of Sytx1 function abolishes Netrin-1-dependent chemoattraction of axons in mouse neuronal cultures and causes defects in commissural axon pathfinding in the chicken spinal cord in vivo.
3
Netrin-1 elicits exocytosis at growth cones in a Sytx1-dependent manner, and the Sytx1/DCC complex associates with the v-SNARE TI-VAMP.

Research Summary

This study identifies a novel signaling mechanism in axonal guidance, where the chemoattractant Netrin-1 and its receptor DCC couple with SNARE proteins (Sytx1 and TI-VAMP) to regulate membrane turnover and exocytosis in growth cones. The interaction between DCC and Sytx1 is Netrin-1 dependent and requires specific domains of both proteins, as evidenced by in vitro and in vivo experiments. Interference with Sytx1 function disrupts Netrin-1-mediated chemoattraction of axons, leading to pathfinding defects reminiscent of Netrin-1 or DCC loss-of-function models.

Practical Implications

Understanding Axonal Guidance

Provides insights into the molecular mechanisms controlling axonal guidance, which is crucial for neural development and regeneration.

Targeting SNARE Proteins

Suggests that SNARE proteins, particularly Sytx1 and TI-VAMP, could be potential therapeutic targets for neurological disorders involving axonal pathfinding defects.

Netrin-1 Signaling

Clarifies the role of Netrin-1 signaling in coordinating chemoattraction and membrane dynamics, contributing to a better understanding of cell migration and development.

A Signaling Mechanism Coupling Netrin-1/Deleted in Colorectal Cancer Chemoattraction to SNARE-Mediated Exocytosis in Axonal Growth Cones

Simple Explanation

Key Findings

Research Summary

Practical Implications

Understanding Axonal Guidance

Targeting SNARE Proteins

Netrin-1 Signaling

Study Limitations

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A Signaling Mechanism Coupling Netrin-1/Deleted in Colorectal Cancer Chemoattraction to SNARE-Mediated Exocytosis in Axonal Growth Cones

Simple Explanation

Key Findings

Research Summary

Practical Implications

Understanding Axonal Guidance

Targeting SNARE Proteins

Netrin-1 Signaling

Study Limitations

Your Feedback

Was this summary helpful?