Transthyretin Promotes Axon Growth via Regulation of Microtubule Dynamics and Tubulin Acetylation

Transthyretin (TTR), a plasma and cerebrospinal fluid protein, increases axon growth and organelle transport in sensory neurons. While neurons extend their axons, the microtubule (MT) cytoskeleton is crucial for the segregation of functional compartments and axonal outgrowth. Herein, we investigated...

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Autores principales:	Jessica Eira, Joana Magalhães, Nídia Macedo, Maria Elena Pero, Thomas Misgeld, Mónica M. Sousa, Francesca Bartolini, Márcia A. Liz
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	transthyretin nerve biology axon growth microtubules tubulin acetylation transthyretin amyloid polyneuropathy Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ce9b46661bcc43f9ac485b03657d5a43
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spelling	oai:doaj.org-article:ce9b46661bcc43f9ac485b03657d5a432021-11-08T06:44:56ZTransthyretin Promotes Axon Growth via Regulation of Microtubule Dynamics and Tubulin Acetylation2296-634X10.3389/fcell.2021.747699https://doaj.org/article/ce9b46661bcc43f9ac485b03657d5a432021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.747699/fullhttps://doaj.org/toc/2296-634XTransthyretin (TTR), a plasma and cerebrospinal fluid protein, increases axon growth and organelle transport in sensory neurons. While neurons extend their axons, the microtubule (MT) cytoskeleton is crucial for the segregation of functional compartments and axonal outgrowth. Herein, we investigated whether TTR promotes axon elongation by modulating MT dynamics. We found that TTR KO mice have an intrinsic increase in dynamic MTs and reduced levels of acetylated α-tubulin in peripheral axons. In addition, they failed to modulate MT dynamics in response to sciatic nerve injury, leading to decreased regenerative capacity. Importantly, restoring acetylated α-tubulin levels of TTR KO dorsal root ganglia (DRG) neurons using an HDAC6 inhibitor is sufficient to completely revert defective MT dynamics and neurite outgrowth. In summary, our results reveal a new role for TTR in the modulation of MT dynamics by regulating α-tubulin acetylation via modulation of the acetylase ATAT1, and suggest that this activity underlies TTR neuritogenic function.Jessica EiraJessica EiraJoana MagalhãesNídia MacedoMaria Elena PeroMaria Elena PeroThomas MisgeldMónica M. SousaFrancesca BartoliniMárcia A. LizFrontiers Media S.A.articletransthyretinnerve biologyaxon growthmicrotubulestubulin acetylationtransthyretin amyloid polyneuropathyBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	transthyretin nerve biology axon growth microtubules tubulin acetylation transthyretin amyloid polyneuropathy Biology (General) QH301-705.5
spellingShingle	transthyretin nerve biology axon growth microtubules tubulin acetylation transthyretin amyloid polyneuropathy Biology (General) QH301-705.5 Jessica Eira Jessica Eira Joana Magalhães Nídia Macedo Maria Elena Pero Maria Elena Pero Thomas Misgeld Mónica M. Sousa Francesca Bartolini Márcia A. Liz Transthyretin Promotes Axon Growth via Regulation of Microtubule Dynamics and Tubulin Acetylation
description	Transthyretin (TTR), a plasma and cerebrospinal fluid protein, increases axon growth and organelle transport in sensory neurons. While neurons extend their axons, the microtubule (MT) cytoskeleton is crucial for the segregation of functional compartments and axonal outgrowth. Herein, we investigated whether TTR promotes axon elongation by modulating MT dynamics. We found that TTR KO mice have an intrinsic increase in dynamic MTs and reduced levels of acetylated α-tubulin in peripheral axons. In addition, they failed to modulate MT dynamics in response to sciatic nerve injury, leading to decreased regenerative capacity. Importantly, restoring acetylated α-tubulin levels of TTR KO dorsal root ganglia (DRG) neurons using an HDAC6 inhibitor is sufficient to completely revert defective MT dynamics and neurite outgrowth. In summary, our results reveal a new role for TTR in the modulation of MT dynamics by regulating α-tubulin acetylation via modulation of the acetylase ATAT1, and suggest that this activity underlies TTR neuritogenic function.
format	article
author	Jessica Eira Jessica Eira Joana Magalhães Nídia Macedo Maria Elena Pero Maria Elena Pero Thomas Misgeld Mónica M. Sousa Francesca Bartolini Márcia A. Liz
author_facet	Jessica Eira Jessica Eira Joana Magalhães Nídia Macedo Maria Elena Pero Maria Elena Pero Thomas Misgeld Mónica M. Sousa Francesca Bartolini Márcia A. Liz
author_sort	Jessica Eira
title	Transthyretin Promotes Axon Growth via Regulation of Microtubule Dynamics and Tubulin Acetylation
title_short	Transthyretin Promotes Axon Growth via Regulation of Microtubule Dynamics and Tubulin Acetylation
title_full	Transthyretin Promotes Axon Growth via Regulation of Microtubule Dynamics and Tubulin Acetylation
title_fullStr	Transthyretin Promotes Axon Growth via Regulation of Microtubule Dynamics and Tubulin Acetylation
title_full_unstemmed	Transthyretin Promotes Axon Growth via Regulation of Microtubule Dynamics and Tubulin Acetylation
title_sort	transthyretin promotes axon growth via regulation of microtubule dynamics and tubulin acetylation
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/ce9b46661bcc43f9ac485b03657d5a43
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Transthyretin Promotes Axon Growth via Regulation of Microtubule Dynamics and Tubulin Acetylation

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