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Published on: February 28, 2019
Negative regulation of fibroblast motility by Ena/VASP proteins
J E Bear1, J J Loureiro, I Libova
1Department of Biology, Massachusetts Institute of Technology, Cambridge, USA.
Abstract:
Ena/VASP proteins have been implicated in cell motility through regulation of the actin cytoskeleton and are found at focal adhesions and the leading edge. Using overexpression, loss-of-function, and inhibitory approaches, we find that Ena/VASP proteins negatively regulate fibroblast motility. A dose-dependent decrease in movement is observed when Ena/VASP proteins are overexpressed in fibroblasts. Neutralization or deletion of all Ena/VASP proteins results in increased cell movement. Selective depletion of Ena/VASP proteins from focal adhesions, but not the leading edge, has no effect on motility. Constitutive membrane targeting of Ena/VASP proteins inhibits motility. These results are in marked contrast to current models for Ena/VASP function derived mainly from their role in the actin-driven movement of Listeria monocytogenes.
Insights
Ena/VASP proteins, crucial for cell movement, were found to hinder fibroblast motility. Their removal increased cell movement, challenging existing models of Ena/VASP function.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Ena/VASP proteins are involved in cell motility by regulating the actin cytoskeleton.
- They are typically found at focal adhesions and the leading edge of cells.
Purpose of the Study:
- To investigate the role of Ena/VASP proteins in fibroblast motility.
- To determine if Ena/VASP proteins positively or negatively regulate cell movement.
Main Methods:
- Overexpression of Ena/VASP proteins in fibroblasts.
- Loss-of-function studies involving neutralization or deletion of Ena/VASP proteins.
- Targeting Ena/VASP proteins to the cell membrane.
Main Results:
- Overexpression of Ena/VASP proteins led to a dose-dependent decrease in fibroblast motility.
- Complete removal or neutralization of Ena/VASP proteins resulted in enhanced cell movement.
- Depleting Ena/VASP proteins from focal adhesions did not affect motility, but constitutive membrane targeting inhibited it.
Conclusions:
- Ena/VASP proteins negatively regulate fibroblast motility, contrary to some established models.
- The localization of Ena/VASP proteins is critical for their function in cell movement.
- Findings contrast with models based on Listeria monocytogenes actin-based motility.
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