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...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2022-04-01
|
Series: | Cells |
Subjects: | |
Online Access: | https://www.mdpi.com/2073-4409/11/9/1487 |
_version_ | 1827672964619829248 |
---|---|
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. |
first_indexed | 2024-03-10T04:16:26Z |
format | Article |
id | doaj.art-d9472d6cdf0d4a27a7b951ed1707acd4 |
institution | Directory Open Access Journal |
issn | 2073-4409 |
language | English |
last_indexed | 2024-03-10T04:16:26Z |
publishDate | 2022-04-01 |
publisher | MDPI AG |
record_format | Article |
series | Cells |
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 |
work_keys_str_mv | AT istvanfoldi moleculardissectionofdaamfunctionduringaxongrowthindrosophilaembryonicneurons AT krisztinatoth moleculardissectionofdaamfunctionduringaxongrowthindrosophilaembryonicneurons AT ritagombos moleculardissectionofdaamfunctionduringaxongrowthindrosophilaembryonicneurons AT petergaszler moleculardissectionofdaamfunctionduringaxongrowthindrosophilaembryonicneurons AT petergorog moleculardissectionofdaamfunctionduringaxongrowthindrosophilaembryonicneurons AT ioanniszygouras moleculardissectionofdaamfunctionduringaxongrowthindrosophilaembryonicneurons AT beatabugyi moleculardissectionofdaamfunctionduringaxongrowthindrosophilaembryonicneurons AT jozsefmihaly moleculardissectionofdaamfunctionduringaxongrowthindrosophilaembryonicneurons |