Ena/VASP Proteins Cooperate with the WAVE Complex to Regulate the Actin Cytoskeleton
| Autor: | Sven Bogdan, Raiko Stephan, Theresa Higgins, Michael K. Rosen, Baoyu Chen, Morag C. Martin, Xing Judy Chen, Anna Julia Squarr, David J. Barry, Michael Way |
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| Jazyk: | angličtina |
| Předmět: |
Proline
WAVE regulatory complex Molecular Sequence Data macromolecular substances Biology Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Cell Movement EVH1 domain Cell Line Tumor Animals Humans Amino Acid Sequence Pseudopodia Molecular Biology Actin 030304 developmental biology 0303 health sciences Sequence Homology Amino Acid Macrophages Gene Expression Regulation Developmental Ena/Vasp homology proteins Cell migration Cell Biology Actin cytoskeleton Axons Protein Structure Tertiary Wiskott-Aldrich Syndrome Protein Family Cell biology DNA-Binding Proteins Actin Cytoskeleton Drosophila melanogaster Photoreceptor Cells Invertebrate Lamellipodium 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Developmental Cell |
| ISSN: | 1534-5807 |
| DOI: | 10.1016/j.devcel.2014.08.001 |
| Popis: | Summary Ena/VASP proteins and the WAVE regulatory complex (WRC) regulate cell motility by virtue of their ability to independently promote actin polymerization. We demonstrate that Ena/VASP and the WRC control actin polymerization in a cooperative manner through the interaction of the Ena/VASP EVH1 domain with an extended proline rich motif in Abi. This interaction increases cell migration and enables VASP to cooperatively enhance WRC stimulation of Arp2/3 complex-mediated actin assembly in vitro in the presence of Rac. Loss of this interaction in Drosophila macrophages results in defects in lamellipodia formation, cell spreading, and redistribution of Ena to the tips of filopodia-like extensions. Rescue experiments of abi mutants also reveals a physiological requirement for the Abi:Ena interaction in photoreceptor axon targeting and oogenesis. Our data demonstrate that the activities of Ena/VASP and the WRC are intimately linked to ensure optimal control of actin polymerization during cell migration and development. Graphical Abstract Highlights • Ena/VASP EVH1 interacts with the Abi subunit of the WRC • VASP enhances the ability of WRC to promote Arp2/3 actin assembly in presence of Rac • Ena/VASP and WRC interactions enhance cell migration • Drosophila photoreceptor axon targeting and oogenesis depends on Ena binding Abi Ena/VASP proteins and the WAVE regulatory complex independently promote actin polymerization. Chen et al. demonstrate that the Ena/VASP EVH1 domain binds Abi in the WRC. This interaction enhances cell migration and Arp2/3-mediated actin polymerization. Loss of this interaction in Drosophila induces changes in macrophage morphology and defects in photoreceptor axon targeting and oogenesis. |
| Databáze: | OpenAIRE |
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