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Mena, a relative of VASP and Drosophila Enabled, is implicated in the control of microfilament dynamics
F B Gertler1, K Niebuhr, M Reinhard
1Division of Molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA.
Abstract:
Drosophila Enabled is required for proper formation of axonal structures and is genetically implicated in signaling pathways mediated by Drosophila AbI. We have identified two murine proteins, Mena and Evl, that are highly related to Enabled as well as VASP (Vasodilator-Stimulated Phosphoprotein). A conserved domain targets Mena to localized proteins containing a specific proline-rich motif. The association of Mena with the surface of the intracellular pathogen Listeria monocytogenes and the G-actin binding protein profilin suggests that this molecule may participate in bacterial movement by facilitating actin polymerization. Expression of neural-enriched isoforms of Mena in fibroblasts induces the formation of abnormal F-actin-rich outgrowths, supporting a role for this protein in microfilament assembly and cell motility.
Insights
Researchers identified Mena and Evl, proteins related to Drosophila Enabled, crucial for cell motility and actin polymerization. These proteins may play a role in bacterial movement and the formation of cellular structures.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Drosophila Enabled is essential for axonal structure formation and implicated in signaling pathways.
- Enabled, Vasodilator-Stimulated Phosphoprotein (VASP), Mena, and Evl are related proteins involved in cytoskeletal regulation.
Purpose of the Study:
- To identify and characterize murine homologs of Drosophila Enabled.
- To investigate the function of Mena and Evl in actin dynamics and cell motility.
Main Methods:
- Protein homology analysis to identify Mena and Evl.
- Biochemical assays to determine Mena's interaction with proline-rich motifs and G-actin binding protein profilin.
- Cell-based assays using fibroblasts expressing neural-enriched Mena isoforms.
Main Results:
- Mena and Evl were identified as murine proteins highly related to Drosophila Enabled and VASP.
- A conserved domain in Mena targets it to proteins with specific proline-rich motifs.
- Mena associates with Listeria monocytogenes and profilin, suggesting a role in actin polymerization for bacterial motility.
- Expression of Mena isoforms in fibroblasts induced abnormal F-actin-rich outgrowths, indicating a role in microfilament assembly.
Conclusions:
- Mena and Evl are functional homologs of Drosophila Enabled.
- Mena plays a significant role in actin dynamics, cell motility, and potentially bacterial movement.
- These findings highlight the conserved function of Enabled family proteins in regulating the actin cytoskeleton.
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