Molecular Dissection of DAAM Function during Axon Growth in Drosophila Embryonic Neurons

Axonal growth is mediated by coordinated changes of the actin and microtubule (MT) cytoskeleton. Ample evidence suggests that members of the formin protein family are involved in the coordination of these cytoskeletal rearrangements, but the molecular mechanisms of the formin-dependent actin–microtu...

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Main Authors: István Földi, Krisztina Tóth, Rita Gombos, Péter Gaszler, Péter Görög, Ioannis Zygouras, Beáta Bugyi, József Mihály
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/11/9/1487
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author István Földi
Krisztina Tóth
Rita Gombos
Péter Gaszler
Péter Görög
Ioannis Zygouras
Beáta Bugyi
József Mihály
author_facet István Földi
Krisztina Tóth
Rita Gombos
Péter Gaszler
Péter Görög
Ioannis Zygouras
Beáta Bugyi
József Mihály
author_sort István Földi
collection DOAJ
description Axonal growth is mediated by coordinated changes of the actin and microtubule (MT) cytoskeleton. Ample evidence suggests that members of the formin protein family are involved in the coordination of these cytoskeletal rearrangements, but the molecular mechanisms of the formin-dependent actin–microtubule crosstalk remains largely elusive. Of the six <i>Drosophila</i> formins, DAAM was shown to play a pivotal role during axonal growth in all stages of nervous system development, while FRL was implicated in axonal development in the adult brain. Here, we aimed to investigate the potentially redundant function of these two formins, and we attempted to clarify which molecular activities are important for axonal growth. We used a combination of genetic analyses, cellular assays and biochemical approaches to demonstrate that the actin-processing activity of DAAM is indispensable for axonal growth in every developmental condition. In addition, we identified a novel MT-binding motif within the FH2 domain of DAAM, which is required for proper growth and guidance of the mushroom body axons, while being dispensable during embryonic axon development. Together, these data suggest that DAAM is the predominant formin during axonal growth in <i>Drosophila</i>, and highlight the contribution of multiple formin-mediated mechanisms in cytoskeleton coordination during axonal growth.
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spelling doaj.art-d9472d6cdf0d4a27a7b951ed1707acd42023-11-23T07:59:53ZengMDPI AGCells2073-44092022-04-01119148710.3390/cells11091487Molecular Dissection of DAAM Function during Axon Growth in Drosophila Embryonic NeuronsIstván Földi0Krisztina Tóth1Rita Gombos2Péter Gaszler3Péter Görög4Ioannis Zygouras5Beáta Bugyi6József Mihály7Biological Research Centre, Institute of Genetics, Eötvös Loránd Research Network, Temesvári krt. 62, H-6726 Szeged, HungaryBiological Research Centre, Institute of Genetics, Eötvös Loránd Research Network, Temesvári krt. 62, H-6726 Szeged, HungaryBiological Research Centre, Institute of Genetics, Eötvös Loránd Research Network, Temesvári krt. 62, H-6726 Szeged, HungaryDepartment of Biophysics, Medical School, University of Pécs, Szigeti str. 12, H-7624 Pécs, HungaryBiological Research Centre, Institute of Genetics, Eötvös Loránd Research Network, Temesvári krt. 62, H-6726 Szeged, HungaryBiological Research Centre, Institute of Genetics, Eötvös Loránd Research Network, Temesvári krt. 62, H-6726 Szeged, HungaryDepartment of Biophysics, Medical School, University of Pécs, Szigeti str. 12, H-7624 Pécs, HungaryBiological Research Centre, Institute of Genetics, Eötvös Loránd Research Network, Temesvári krt. 62, H-6726 Szeged, HungaryAxonal growth is mediated by coordinated changes of the actin and microtubule (MT) cytoskeleton. Ample evidence suggests that members of the formin protein family are involved in the coordination of these cytoskeletal rearrangements, but the molecular mechanisms of the formin-dependent actin–microtubule crosstalk remains largely elusive. Of the six <i>Drosophila</i> formins, DAAM was shown to play a pivotal role during axonal growth in all stages of nervous system development, while FRL was implicated in axonal development in the adult brain. Here, we aimed to investigate the potentially redundant function of these two formins, and we attempted to clarify which molecular activities are important for axonal growth. We used a combination of genetic analyses, cellular assays and biochemical approaches to demonstrate that the actin-processing activity of DAAM is indispensable for axonal growth in every developmental condition. In addition, we identified a novel MT-binding motif within the FH2 domain of DAAM, which is required for proper growth and guidance of the mushroom body axons, while being dispensable during embryonic axon development. Together, these data suggest that DAAM is the predominant formin during axonal growth in <i>Drosophila</i>, and highlight the contribution of multiple formin-mediated mechanisms in cytoskeleton coordination during axonal growth.https://www.mdpi.com/2073-4409/11/9/1487cytoskeletonforminaxonnervous systemdevelopmentDrosophila
spellingShingle István Földi
Krisztina Tóth
Rita Gombos
Péter Gaszler
Péter Görög
Ioannis Zygouras
Beáta Bugyi
József Mihály
Molecular Dissection of DAAM Function during Axon Growth in Drosophila Embryonic Neurons
Cells
cytoskeleton
formin
axon
nervous system
development
Drosophila
title Molecular Dissection of DAAM Function during Axon Growth in Drosophila Embryonic Neurons
title_full Molecular Dissection of DAAM Function during Axon Growth in Drosophila Embryonic Neurons
title_fullStr Molecular Dissection of DAAM Function during Axon Growth in Drosophila Embryonic Neurons
title_full_unstemmed Molecular Dissection of DAAM Function during Axon Growth in Drosophila Embryonic Neurons
title_short Molecular Dissection of DAAM Function during Axon Growth in Drosophila Embryonic Neurons
title_sort molecular dissection of daam function during axon growth in drosophila embryonic neurons
topic cytoskeleton
formin
axon
nervous system
development
Drosophila
url https://www.mdpi.com/2073-4409/11/9/1487
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