Enabled Negatively Regulates Diaphanous-Driven Actin Dynamics In Vitro and In Vivo
| Autor: | Timothy C. Elston, Denis Tsygankov, Mark Peifer, David R. Kovar, Vinal V. Lakhani, Kate Comber, Stephanie H. Nowotarski, Will J Wood, Colleen G. Bilancia, Jennifer A. Sees, Iwan Robert Evans, Jonathan D. Winkelman |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Hemocytes
Morphogenesis Formins Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine Cell Movement Animals Drosophila Proteins Pseudopodia Molecular Biology Actin 030304 developmental biology 0303 health sciences Ena/Vasp homology proteins Cell migration Cell Biology Actins 3. Good health Cell biology DNA-Binding Proteins Hemocyte migration Drosophila melanogaster Cell culture Carrier Proteins Filopodia 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Developmental Cell |
| ISSN: | 1878-1551 1534-5807 |
| Popis: | Summary Actin regulators facilitate cell migration by controlling cell protrusion architecture and dynamics. As the behavior of individual actin regulators becomes clear, we must address why cells require multiple regulators with similar functions and how they cooperate to create diverse protrusions. We characterized Diaphanous (Dia) and Enabled (Ena) as a model, using complementary approaches: cell culture, biophysical analysis, and Drosophila morphogenesis. We found that Dia and Ena have distinct biochemical properties that contribute to the different protrusion morphologies each induces. Dia is a more processive, faster elongator, paralleling the long, stable filopodia it induces in vivo, while Ena promotes filopodia with more dynamic changes in number, length, and lifetime. Acting together, Ena and Dia induce protrusions distinct from those induced by either alone, with Ena reducing Dia-driven protrusion length and number. Consistent with this, EnaEVH1 binds Dia directly and inhibits DiaFH1FH2-mediated nucleation in vitro. Finally, Ena rescues hemocyte migration defects caused by activated Dia. Graphical Abstract Highlights • Dia and Ena differ biochemically, promoting distinct filopodia dynamics • Dia and Ena colocalization negatively regulates filopodia • Ena’s EVH1 binds Dia’s FH1 and reduces Dia-driven filopodia and actin nucleation • Ena rescues DiaΔDAD inhibition of hemocyte migration speed to wounds in vivo Bilancia et al. show that the actin regulators Dia and Ena differ biochemically and produce distinct protrusions. Dia is more processive and forms stable filopodia. Ena promotes dynamic filopodia. Dia and Ena directly bind each other, modulating their activities. Ena reduces Dia-driven filopodia, actin nucleation, and effects on cell migration. |
| Databáze: | OpenAIRE |
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