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

Nye, Derek M. R. and Albertson, Richard M. and Weiner, Alexis T. and Hertzler, J. Ian and Shorey, Matthew and Goberdhan, Deborah C. I. and Wilson, Clive and Janes, Kevin A. and Rolls, Melissa M. and Akhmanova, Anna (2020) The receptor tyrosine kinase Ror is required for dendrite regeneration in Drosophila neurons. PLOS Biology, 18 (3). e3000657. ISSN 1545-7885

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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.

Item Type: Article
Subjects: Euro Archives > Biological Science
Depositing User: Managing Editor
Date Deposited: 30 Jan 2023 04:20
Last Modified: 30 Jan 2023 04:20

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