Cargando…

Nicotinamide adenine dinucleotides and their precursor NMN have no direct effect on microtubule dynamics in purified brain tubulin

Microtubules are dynamic cytoskeletal polymers that provide mechanical support for cellular structures, and play important roles in cell division, migration, and intracellular transport. Their intrinsic dynamic instability, primarily controlled by polymerization-dependent GTP hydrolysis, allows for...

Descripción completa

Detalles Bibliográficos
Autores principales: Luchniak, Anna, Mahamdeh, Mohammed, Howard, Jonathon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687165/
https://www.ncbi.nlm.nih.gov/pubmed/31393939
http://dx.doi.org/10.1371/journal.pone.0220794
_version_ 1783442690618163200
author Luchniak, Anna
Mahamdeh, Mohammed
Howard, Jonathon
author_facet Luchniak, Anna
Mahamdeh, Mohammed
Howard, Jonathon
author_sort Luchniak, Anna
collection PubMed
description Microtubules are dynamic cytoskeletal polymers that provide mechanical support for cellular structures, and play important roles in cell division, migration, and intracellular transport. Their intrinsic dynamic instability, primarily controlled by polymerization-dependent GTP hydrolysis, allows for rapid rearrangements of microtubule arrays in response to signaling cues. In neurons, increases in intracellular levels of nicotinamide adenine dinucleotide (NAD(+)) can protect against microtubule loss and axonal degeneration elicited by axonal transection. The protective effects of NAD(+) on microtubule loss have been shown to be indirect in some systems, for example through the sirtuin-3 pathway. However, it is still possible that NAD(+) and related metabolites have direct effects on microtubule dynamics to promote assembly or inhibit disassembly. To address this question, we reconstituted microtubule dynamics in an in vitro assay with purified bovine brain tubulin and examined the effects of NAD(+), NADH, and NMN. We found that the compounds had only small effects on the dynamics at the plus and minus ends of the microtubules. Furthermore, these effects were not statistically significant. Consequently, our data support earlier findings that NADs and their precursors influence microtubule growth through indirect mechanisms.
format Online
Article
Text
id pubmed-6687165
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-66871652019-08-15 Nicotinamide adenine dinucleotides and their precursor NMN have no direct effect on microtubule dynamics in purified brain tubulin Luchniak, Anna Mahamdeh, Mohammed Howard, Jonathon PLoS One Research Article Microtubules are dynamic cytoskeletal polymers that provide mechanical support for cellular structures, and play important roles in cell division, migration, and intracellular transport. Their intrinsic dynamic instability, primarily controlled by polymerization-dependent GTP hydrolysis, allows for rapid rearrangements of microtubule arrays in response to signaling cues. In neurons, increases in intracellular levels of nicotinamide adenine dinucleotide (NAD(+)) can protect against microtubule loss and axonal degeneration elicited by axonal transection. The protective effects of NAD(+) on microtubule loss have been shown to be indirect in some systems, for example through the sirtuin-3 pathway. However, it is still possible that NAD(+) and related metabolites have direct effects on microtubule dynamics to promote assembly or inhibit disassembly. To address this question, we reconstituted microtubule dynamics in an in vitro assay with purified bovine brain tubulin and examined the effects of NAD(+), NADH, and NMN. We found that the compounds had only small effects on the dynamics at the plus and minus ends of the microtubules. Furthermore, these effects were not statistically significant. Consequently, our data support earlier findings that NADs and their precursors influence microtubule growth through indirect mechanisms. Public Library of Science 2019-08-08 /pmc/articles/PMC6687165/ /pubmed/31393939 http://dx.doi.org/10.1371/journal.pone.0220794 Text en © 2019 Luchniak 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
Luchniak, Anna
Mahamdeh, Mohammed
Howard, Jonathon
Nicotinamide adenine dinucleotides and their precursor NMN have no direct effect on microtubule dynamics in purified brain tubulin
title Nicotinamide adenine dinucleotides and their precursor NMN have no direct effect on microtubule dynamics in purified brain tubulin
title_full Nicotinamide adenine dinucleotides and their precursor NMN have no direct effect on microtubule dynamics in purified brain tubulin
title_fullStr Nicotinamide adenine dinucleotides and their precursor NMN have no direct effect on microtubule dynamics in purified brain tubulin
title_full_unstemmed Nicotinamide adenine dinucleotides and their precursor NMN have no direct effect on microtubule dynamics in purified brain tubulin
title_short Nicotinamide adenine dinucleotides and their precursor NMN have no direct effect on microtubule dynamics in purified brain tubulin
title_sort nicotinamide adenine dinucleotides and their precursor nmn have no direct effect on microtubule dynamics in purified brain tubulin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687165/
https://www.ncbi.nlm.nih.gov/pubmed/31393939
http://dx.doi.org/10.1371/journal.pone.0220794
work_keys_str_mv AT luchniakanna nicotinamideadeninedinucleotidesandtheirprecursornmnhavenodirecteffectonmicrotubuledynamicsinpurifiedbraintubulin
AT mahamdehmohammed nicotinamideadeninedinucleotidesandtheirprecursornmnhavenodirecteffectonmicrotubuledynamicsinpurifiedbraintubulin
AT howardjonathon nicotinamideadeninedinucleotidesandtheirprecursornmnhavenodirecteffectonmicrotubuledynamicsinpurifiedbraintubulin