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- Publisher Website: 10.1091/mbc.E17-06-0424
- Scopus: eid_2-s2.0-85031280281
- PMID: 28835377
- WOS: WOS:000414550500005
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Article: Distinct effects of tubulin isotype mutations on neurite growth in Caenorhabditis elegans
Title | Distinct effects of tubulin isotype mutations on neurite growth in Caenorhabditis elegans |
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Authors | |
Issue Date | 2017 |
Citation | Molecular Biology of the Cell, 2017, v. 28, n. 21, p. 2786-2801 How to Cite? |
Abstract | © 2017 Schvartz et al. Tubulins, the building block of microtubules (MTs), play a critical role in both supporting and regulating neurite growth. Eukaryotic genomes contain multiple tubulin isotypes, and their missense mutations cause a range of neurodevelopmental defects. Using the Caenorhabditis elegans touch receptor neurons, we analyzed the effects of 67 tubulin missense mutations on neurite growth. Three types of mutations emerged: 1) loss-of-function mutations, which cause mild defects in neurite growth; 2) antimorphic mutations, which map to the GTP binding site and intradimer and interdimer interfaces, significantly reduce MT stability, and cause severe neurite growth defects; and 3) neomorphic mutations, which map to the exterior surface, increase MT stability, and cause ectopic neurite growth. Structure-function analysis reveals a causal relationship between tubulin structure and MT stability. This stability affects neuronal morphogenesis. As part of this analysis, we engineered several disease-associated human tubulin mutations into C. Elegans genes and examined their impact on neuronal development at the cellular level. We also discovered an α-tubulin (TBA-7) that appears to destabilize MTs. Loss of TBA-7 led to the formation of hyperstable MTs and the generation of ectopic neurites; the lack of potential sites for polyamination and polyglutamination on TBA- 7 may be responsible for this destabilization. |
Persistent Identifier | http://hdl.handle.net/10722/265719 |
ISSN | 2023 Impact Factor: 3.1 2023 SCImago Journal Rankings: 1.566 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Zheng, Chaogu | - |
dc.contributor.author | Diaz-Cuadros, Margarete | - |
dc.contributor.author | Nguyen, Ken C.Q. | - |
dc.contributor.author | Hall, David H. | - |
dc.contributor.author | Chalfie, Martin | - |
dc.date.accessioned | 2018-12-03T01:21:29Z | - |
dc.date.available | 2018-12-03T01:21:29Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Molecular Biology of the Cell, 2017, v. 28, n. 21, p. 2786-2801 | - |
dc.identifier.issn | 1059-1524 | - |
dc.identifier.uri | http://hdl.handle.net/10722/265719 | - |
dc.description.abstract | © 2017 Schvartz et al. Tubulins, the building block of microtubules (MTs), play a critical role in both supporting and regulating neurite growth. Eukaryotic genomes contain multiple tubulin isotypes, and their missense mutations cause a range of neurodevelopmental defects. Using the Caenorhabditis elegans touch receptor neurons, we analyzed the effects of 67 tubulin missense mutations on neurite growth. Three types of mutations emerged: 1) loss-of-function mutations, which cause mild defects in neurite growth; 2) antimorphic mutations, which map to the GTP binding site and intradimer and interdimer interfaces, significantly reduce MT stability, and cause severe neurite growth defects; and 3) neomorphic mutations, which map to the exterior surface, increase MT stability, and cause ectopic neurite growth. Structure-function analysis reveals a causal relationship between tubulin structure and MT stability. This stability affects neuronal morphogenesis. As part of this analysis, we engineered several disease-associated human tubulin mutations into C. Elegans genes and examined their impact on neuronal development at the cellular level. We also discovered an α-tubulin (TBA-7) that appears to destabilize MTs. Loss of TBA-7 led to the formation of hyperstable MTs and the generation of ectopic neurites; the lack of potential sites for polyamination and polyglutamination on TBA- 7 may be responsible for this destabilization. | - |
dc.language | eng | - |
dc.relation.ispartof | Molecular Biology of the Cell | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | Distinct effects of tubulin isotype mutations on neurite growth in Caenorhabditis elegans | - |
dc.type | Article | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1091/mbc.E17-06-0424 | - |
dc.identifier.pmid | 28835377 | - |
dc.identifier.scopus | eid_2-s2.0-85031280281 | - |
dc.identifier.volume | 28 | - |
dc.identifier.issue | 21 | - |
dc.identifier.spage | 2786 | - |
dc.identifier.epage | 2801 | - |
dc.identifier.eissn | 1939-4586 | - |
dc.identifier.isi | WOS:000414550500005 | - |
dc.identifier.issnl | 1059-1524 | - |