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Ena/VASP proteins mediate repulsion from ephrin ligands
Iwan R Evans1, Thomas Renne, Frank B Gertler
1Department of Biochemistry, School of Medical Sciences, University of Bristol, University Walk, Bristol, BS8 1TD, UK.
Journal of Cell Science
|December 21, 2006
Summary
Ena/VASP proteins destabilize cell protrusions, impacting repulsion from ephrin guidance cues. This study reveals their role in Eph receptor signaling and cell migration during development.
Area of Science:
- Cell Biology
- Developmental Biology
- Neuroscience
Background:
- Ena/VASP proteins regulate cell motility and repulsion from guidance cues.
- Eph receptors mediate repulsion from ephrins during developmental cell migrations.
- Ephrin-B expression in somites restricts neural crest cell migration.
Purpose of the Study:
- To investigate the role of Ena/VASP proteins downstream of Eph receptors.
- To determine how Ena/VASP proteins affect neural crest cell lamellipodia stability in response to ephrins.
- To elucidate the mechanism by which Ena/VASP proteins contribute to ephrin-induced repulsion.
Main Methods:
- Timelapse microscopy to observe cell behavior and lamellipodia dynamics.
- Functional assays using Ena/VASP-deficient fibroblasts and wild-type controls.
- Co-expression of EphB4 and ephrin-B2 in Swiss 3T3 fibroblasts to study receptor-protein interactions.
Main Results:
- Ephrin-B2 destabilizes neural crest cell lamellipodia, causing rearward collapse and membrane ruffling.
- Ena/VASP-deficient fibroblasts show reduced repulsion from ephrin-A and ephrin-B stripes.
- VASP and Mena co-accumulate with activated Eph receptors, and their sequestration inhibits Eph receptor internalization.
Conclusions:
- Ena/VASP proteins destabilize cellular protrusions, contributing to repulsion from ephrins.
- Ena/VASP proteins regulate Eph receptor signaling downstream of ephrin binding.
- These findings suggest a novel mechanism for Ena/VASP proteins in guiding cell migration during development.
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