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The receptor tyrosine kinase Ror is required for dendrite regeneration in Drosophila neurons

While many regulators of axon regeneration have been identified, very little is known about mechanisms that allow dendrites to regenerate after injury. Using a Drosophila model of dendrite regeneration, we performed a candidate screen of receptor tyrosine kinases (RTKs) and found a requirement for R...

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Autores principales: Nye, Derek M. R., Albertson, Richard M., Weiner, Alexis T., Hertzler, J. Ian, Shorey, Matthew, Goberdhan, Deborah C. I., Wilson, Clive, Janes, Kevin A., Rolls, Melissa M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067388/
https://www.ncbi.nlm.nih.gov/pubmed/32163406
http://dx.doi.org/10.1371/journal.pbio.3000657
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author Nye, Derek M. R.
Albertson, Richard M.
Weiner, Alexis T.
Hertzler, J. Ian
Shorey, Matthew
Goberdhan, Deborah C. I.
Wilson, Clive
Janes, Kevin A.
Rolls, Melissa M.
author_facet Nye, Derek M. R.
Albertson, Richard M.
Weiner, Alexis T.
Hertzler, J. Ian
Shorey, Matthew
Goberdhan, Deborah C. I.
Wilson, Clive
Janes, Kevin A.
Rolls, Melissa M.
author_sort Nye, Derek M. R.
collection PubMed
description While many regulators of axon regeneration have been identified, very little is known about mechanisms that allow dendrites to regenerate after injury. Using a Drosophila model of dendrite regeneration, we performed a candidate screen of receptor tyrosine kinases (RTKs) and found a requirement for RTK-like orphan receptor (Ror). We confirmed that Ror was required for regeneration in two different neuron types using RNA interference (RNAi) and mutants. Ror was not required for axon regeneration or normal dendrite development, suggesting a specific role in dendrite regeneration. Ror can act as a Wnt coreceptor with frizzleds (fzs) in other contexts, so we tested the involvement of Wnt signaling proteins in dendrite regeneration. We found that knockdown of fz, dishevelled (dsh), Axin, and gilgamesh (gish) also reduced dendrite regeneration. Moreover, Ror was required to position dsh and Axin in dendrites. We recently found that Wnt signaling proteins, including dsh and Axin, localize microtubule nucleation machinery in dendrites. We therefore hypothesized that Ror may act by regulating microtubule nucleation at baseline and during dendrite regeneration. Consistent with this hypothesis, localization of the core nucleation protein γTubulin was reduced in Ror RNAi neurons, and this effect was strongest during dendrite regeneration. In addition, dendrite regeneration was sensitive to partial reduction of γTubulin. We conclude that Ror promotes dendrite regeneration as part of a Wnt signaling pathway that regulates dendritic microtubule nucleation.
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spelling pubmed-70673882020-03-23 The receptor tyrosine kinase Ror is required for dendrite regeneration in Drosophila neurons Nye, Derek M. R. Albertson, Richard M. Weiner, Alexis T. Hertzler, J. Ian Shorey, Matthew Goberdhan, Deborah C. I. Wilson, Clive Janes, Kevin A. Rolls, Melissa M. PLoS Biol Research Article While many regulators of axon regeneration have been identified, very little is known about mechanisms that allow dendrites to regenerate after injury. Using a Drosophila model of dendrite regeneration, we performed a candidate screen of receptor tyrosine kinases (RTKs) and found a requirement for RTK-like orphan receptor (Ror). We confirmed that Ror was required for regeneration in two different neuron types using RNA interference (RNAi) and mutants. Ror was not required for axon regeneration or normal dendrite development, suggesting a specific role in dendrite regeneration. Ror can act as a Wnt coreceptor with frizzleds (fzs) in other contexts, so we tested the involvement of Wnt signaling proteins in dendrite regeneration. We found that knockdown of fz, dishevelled (dsh), Axin, and gilgamesh (gish) also reduced dendrite regeneration. Moreover, Ror was required to position dsh and Axin in dendrites. We recently found that Wnt signaling proteins, including dsh and Axin, localize microtubule nucleation machinery in dendrites. We therefore hypothesized that Ror may act by regulating microtubule nucleation at baseline and during dendrite regeneration. Consistent with this hypothesis, localization of the core nucleation protein γTubulin was reduced in Ror RNAi neurons, and this effect was strongest during dendrite regeneration. In addition, dendrite regeneration was sensitive to partial reduction of γTubulin. We conclude that Ror promotes dendrite regeneration as part of a Wnt signaling pathway that regulates dendritic microtubule nucleation. Public Library of Science 2020-03-12 /pmc/articles/PMC7067388/ /pubmed/32163406 http://dx.doi.org/10.1371/journal.pbio.3000657 Text en © 2020 Nye et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Nye, Derek M. R.
Albertson, Richard M.
Weiner, Alexis T.
Hertzler, J. Ian
Shorey, Matthew
Goberdhan, Deborah C. I.
Wilson, Clive
Janes, Kevin A.
Rolls, Melissa M.
The receptor tyrosine kinase Ror is required for dendrite regeneration in Drosophila neurons
title The receptor tyrosine kinase Ror is required for dendrite regeneration in Drosophila neurons
title_full The receptor tyrosine kinase Ror is required for dendrite regeneration in Drosophila neurons
title_fullStr The receptor tyrosine kinase Ror is required for dendrite regeneration in Drosophila neurons
title_full_unstemmed The receptor tyrosine kinase Ror is required for dendrite regeneration in Drosophila neurons
title_short The receptor tyrosine kinase Ror is required for dendrite regeneration in Drosophila neurons
title_sort receptor tyrosine kinase ror is required for dendrite regeneration in drosophila neurons
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067388/
https://www.ncbi.nlm.nih.gov/pubmed/32163406
http://dx.doi.org/10.1371/journal.pbio.3000657
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