Qu, Yue, Alves-Silva, Juliana, Gupta, Kriti et al. (4 more authors) (2022) Re-evaluating the actin-dependence of spectraplakin functions during axon growth and maintenance. Developmental Neurobiology. ISSN 1932-846X
Abstract
Axons are the long and slender processes of neurons constituting the biological cables that wire the nervous system. The growth and maintenance of axons require loose microtubule bundles that extend through their entire length. Understanding microtubule regulation is therefore an essential aspect of axon biology. Key regulators of neuronal microtubules are the spectraplakins, a well-conserved family of cytoskeletal cross-linkers that underlie neuropathies in mouse and humans. Spectraplakin deficiency in mouse or Drosophila causes severe decay of microtubule bundles and reduced axon growth. The underlying mechanisms are best understood for Drosophila's spectraplakin Short stop (Shot) and believed to involve cytoskeletal cross-linkage: Shot's binding to microtubules and Eb1 via its C-terminus has been thoroughly investigated, whereas its F-actin interaction via N-terminal calponin homology (CH) domains is little understood. Here we have gained new understanding by showing that the F-actin interaction must be finely balanced: altering the properties of F-actin networks or deleting/exchanging Shot's CH domains induces changes in Shot function - with a Lifeact-containing Shot variant causing remarkable remodelling of neuronal microtubules. In addition to actin-MT cross-linkage, we find strong indications that Shot executes redundant MT bundle-promoting roles that are F-actin-independent. We argue that these likely involve the neuronal Shot-PH isoform, which is characterised by a large, unexplored central plakin repeat region (PRR) similarly existing also in mammalian spectraplakins.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 The Authors. |
Keywords: | Drosophila,axons,microtubules,actin,neurodevelopment,genetic tools |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 21 Jun 2022 16:50 |
Last Modified: | 08 Feb 2025 00:46 |
Published Version: | https://doi.org/10.1002/dneu.22873 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1002/dneu.22873 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:188303 |
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Description: Developmental Neurobiology - 2022 - Qu - Re‐evaluating the actin‐dependence of spectraplakin functions during axon growth
Licence: CC-BY 2.5