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Differential modification of the C-terminal tails of different α-tubulins and their importance for microtubule function in vivo

Microtubules (MTs) are built from α-/β-tubulin dimers and used as tracks by kinesin and dynein motors to transport a variety of cargos, such as mRNAs, proteins, and organelles, within the cell. Tubulins are subjected to several post-translational modifications (PTMs). Glutamylation is one of them, a...

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Autores principales: Bao, Mengjing, Dörig, Ruth E, Vazquez-Pianzola, Paula Maria, Beuchle, Dirk, Suter, Beat
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10335831/
https://www.ncbi.nlm.nih.gov/pubmed/37345829
http://dx.doi.org/10.7554/eLife.87125
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author Bao, Mengjing
Dörig, Ruth E
Vazquez-Pianzola, Paula Maria
Beuchle, Dirk
Suter, Beat
author_facet Bao, Mengjing
Dörig, Ruth E
Vazquez-Pianzola, Paula Maria
Beuchle, Dirk
Suter, Beat
author_sort Bao, Mengjing
collection PubMed
description Microtubules (MTs) are built from α-/β-tubulin dimers and used as tracks by kinesin and dynein motors to transport a variety of cargos, such as mRNAs, proteins, and organelles, within the cell. Tubulins are subjected to several post-translational modifications (PTMs). Glutamylation is one of them, and it is responsible for adding one or more glutamic acid residues as branched peptide chains to the C-terminal tails of both α- and β-tubulin. However, very little is known about the specific modifications found on the different tubulin isotypes in vivo and the role of these PTMs in MT transport and other cellular processes in vivo. In this study, we found that in Drosophila ovaries, glutamylation of α-tubulin isotypes occurred clearly on the C-terminal ends of αTub84B and αTub84D (αTub84B/D). In contrast, the ovarian α-tubulin, αTub67C, is not glutamylated. The C-terminal ends of αTub84B/D are glutamylated at several glutamyl sidechains in various combinations. Drosophila TTLL5 is required for the mono- and poly-glutamylation of ovarian αTub84B/D and with this for the proper localization of glutamylated microtubules. Similarly, the normal distribution of kinesin-1 in the germline relies on TTLL5. Next, two kinesin-1-dependent processes, the precise localization of Staufen and the fast, bidirectional ooplasmic streaming, depend on TTLL5, too, suggesting a causative pathway. In the nervous system, a mutation of TTLL5 that inactivates its enzymatic activity decreases the pausing of anterograde axonal transport of mitochondria. Our results demonstrate in vivo roles of TTLL5 in differential glutamylation of α-tubulins and point to the in vivo importance of α-tubulin glutamylation for cellular functions involving microtubule transport.
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spelling pubmed-103358312023-07-12 Differential modification of the C-terminal tails of different α-tubulins and their importance for microtubule function in vivo Bao, Mengjing Dörig, Ruth E Vazquez-Pianzola, Paula Maria Beuchle, Dirk Suter, Beat eLife Cell Biology Microtubules (MTs) are built from α-/β-tubulin dimers and used as tracks by kinesin and dynein motors to transport a variety of cargos, such as mRNAs, proteins, and organelles, within the cell. Tubulins are subjected to several post-translational modifications (PTMs). Glutamylation is one of them, and it is responsible for adding one or more glutamic acid residues as branched peptide chains to the C-terminal tails of both α- and β-tubulin. However, very little is known about the specific modifications found on the different tubulin isotypes in vivo and the role of these PTMs in MT transport and other cellular processes in vivo. In this study, we found that in Drosophila ovaries, glutamylation of α-tubulin isotypes occurred clearly on the C-terminal ends of αTub84B and αTub84D (αTub84B/D). In contrast, the ovarian α-tubulin, αTub67C, is not glutamylated. The C-terminal ends of αTub84B/D are glutamylated at several glutamyl sidechains in various combinations. Drosophila TTLL5 is required for the mono- and poly-glutamylation of ovarian αTub84B/D and with this for the proper localization of glutamylated microtubules. Similarly, the normal distribution of kinesin-1 in the germline relies on TTLL5. Next, two kinesin-1-dependent processes, the precise localization of Staufen and the fast, bidirectional ooplasmic streaming, depend on TTLL5, too, suggesting a causative pathway. In the nervous system, a mutation of TTLL5 that inactivates its enzymatic activity decreases the pausing of anterograde axonal transport of mitochondria. Our results demonstrate in vivo roles of TTLL5 in differential glutamylation of α-tubulins and point to the in vivo importance of α-tubulin glutamylation for cellular functions involving microtubule transport. eLife Sciences Publications, Ltd 2023-06-22 /pmc/articles/PMC10335831/ /pubmed/37345829 http://dx.doi.org/10.7554/eLife.87125 Text en © 2023, Bao et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Bao, Mengjing
Dörig, Ruth E
Vazquez-Pianzola, Paula Maria
Beuchle, Dirk
Suter, Beat
Differential modification of the C-terminal tails of different α-tubulins and their importance for microtubule function in vivo
title Differential modification of the C-terminal tails of different α-tubulins and their importance for microtubule function in vivo
title_full Differential modification of the C-terminal tails of different α-tubulins and their importance for microtubule function in vivo
title_fullStr Differential modification of the C-terminal tails of different α-tubulins and their importance for microtubule function in vivo
title_full_unstemmed Differential modification of the C-terminal tails of different α-tubulins and their importance for microtubule function in vivo
title_short Differential modification of the C-terminal tails of different α-tubulins and their importance for microtubule function in vivo
title_sort differential modification of the c-terminal tails of different α-tubulins and their importance for microtubule function in vivo
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10335831/
https://www.ncbi.nlm.nih.gov/pubmed/37345829
http://dx.doi.org/10.7554/eLife.87125
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