Related Experiment Video

Updated: Aug 21, 2026

Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion
09:23

Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion

Published on: April 2, 2020

Activation of FAK and Src are receptor-proximal events required for netrin signaling

Weiquan Li1, Jeeyong Lee, Haris G Vikis

  • 1Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.

Nature Neuroscience
|October 21, 2004
PubMed

Insights

Netrin receptor DCC interacts with Src and FAK kinases. This interaction is crucial for netrin-mediated axon guidance during neuronal development, highlighting a new signaling pathway.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Signaling

Background:

  • Netrin is a key axon guidance cue essential for neuronal development.
  • Deleted in colorectal cancer (DCC) is a known netrin receptor mediating axon outgrowth and steering.

Purpose of the Study:

  • To elucidate the molecular mechanism by which DCC mediates netrin signaling.
  • To identify downstream signaling molecules interacting with DCC.

Main Methods:

  • Co-immunoprecipitation to study protein interactions.
  • Inhibition of Src family kinases.
  • Site-directed mutagenesis of DCC phosphorylation sites.
  • Neuronal culture and axon guidance assays.

Main Results:

  • DCC's intracellular domain directly interacts with Src and FAK tyrosine kinases.
  • Netrin binding to DCC activates FAK and Src, leading to DCC tyrosine phosphorylation.
  • Inhibition of Src kinases blocks netrin-induced DCC phosphorylation and axon guidance.
  • Mutating DCC's tyrosine phosphorylation site abolishes netrin-induced axon attraction.

Conclusions:

  • DCC functions as a kinase-coupled receptor in netrin signaling.
  • FAK and Src act downstream of DCC to mediate netrin's effects on axon guidance.
  • This study reveals a novel signaling pathway critical for neuronal development.

More Related Videos

Analyses of Actin Dynamics, Clutch Coupling and Traction Force for Growth Cone Advance07:53

Analyses of Actin Dynamics, Clutch Coupling and Traction Force for Growth Cone Advance

Published on: October 21, 2021

Labeling F-actin Barbed Ends with Rhodamine-actin in Permeabilized Neuronal Growth Cones09:14

Labeling F-actin Barbed Ends with Rhodamine-actin in Permeabilized Neuronal Growth Cones

Published on: March 17, 2011

Related Concept Videos

Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
Cell Polarization by Rho Proteins01:21

Cell Polarization by Rho Proteins

Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...