Effects of αTAT1 and HDAC5 on axonal regeneration in adult neurons

PloS One
Shen LinGeorge M Smith

Abstract

The role of posttranslational modifications in axonal injury and regeneration has been widely studied but there has been little consensus over the mechanism by which each modification affects adult axonal growth. Acetylation is known to play an important role in a variety of neuronal functions and its homeostasis is controlled by two enzyme families: the Histone Deacetylases (HDACs) and Histone Acetyl Transferases (HATs). Recent studies show that HDAC5 deacetylates microtubules in the axonal cytoplasm as part of an injury-induced regeneration response, but little is known about how acetylation of microtubules plays a role. Alpha-tubulin acetyl transferase (αTAT1) is a microtubule specific acetyl transferase that binds to microtubules and directly affects microtubule stability in cells. We hypothesize that increasing tubulin acetylation may play an important role in increasing the rate of axonal growth. In this study, we infected cultured adult DRG neurons with αTAT1 and αTAT1-D157N, a catalytically inactive mutant, and HDAC5, using lentiviruses. We found that αTAT1 significantly increases tubulin acetylation in 293T cells and DRG neurons but αTAT1-D157N does not. Furthermore, in neurons infected with αTAT1, a significant increa...Continue Reading

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Citations

Mar 24, 2018·Archives of Insect Biochemistry and Physiology·Huaixiang ZhouZuoming Nie
Jul 29, 2020·Frontiers in Cellular Neuroscience·William RodemerMichael E Selzer
Nov 15, 2020·International Journal of Molecular Sciences·Hiroki KazamaYasufumi Murakami
Jan 21, 2021·Proceedings of the National Academy of Sciences of the United States of America·Maria Elena PeroFrancesca Bartolini

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Methods Mentioned

BETA
acetylation
histone acetylation
PCR
transfection
ELISA
mechanical dissociation
Infrared Imaging
PMA
acetylates

Software Mentioned

ImageJ
Graphpad Prism
GENEWIZ
LI
COR Image Studio

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