ATAT1-enriched Vesicles Promote Microtubule Acetylation Via Axonal Transport

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2020 Jan 4

PMID 31897425

Citations 33

Authors

Aviel Even

Giovanni Morelli

Loic Broix

Chiara Scaramuzzino

Silvia Turchetto

Ivan Gladwyn-Ng

Romain Le Bail

Michal Shilian

Stephen Freeman

Maria M Magiera

A S Jijumon

Nathalie Krusy

Brigitte Malgrange

Bert Brone

Paula Dietrich

Ioannis Dragatsis

Carsten Janke

Frederic Saudou

Miguel Weil

Laurent Nguyen

Affiliations

Soon will be listed here.

Abstract

Microtubules are polymerized dimers of α- and β-tubulin that underlie a broad range of cellular activities. Acetylation of α-tubulin by the acetyltransferase ATAT1 modulates microtubule dynamics and functions in neurons. However, it remains unclear how this enzyme acetylates microtubules over long distances in axons. Here, we show that loss of ATAT1 impairs axonal transport in neurons in vivo, and cell-free motility assays confirm a requirement of α-tubulin acetylation for proper bidirectional vesicular transport. Moreover, we demonstrate that the main cellular pool of ATAT1 is transported at the cytosolic side of neuronal vesicles that are moving along axons. Together, our data suggest that axonal transport of ATAT1-enriched vesicles is the predominant driver of α-tubulin acetylation in axons.

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References

Shida T, Cueva J, Xu Z, Goodman M, Nachury M . The major alpha-tubulin K40 acetyltransferase alphaTAT1 promotes rapid ciliogenesis and efficient mechanosensation. Proc Natl Acad Sci U S A. 2010; 107(50):21517-22. PMC: 3003046. DOI: 10.1073/pnas.1013728107. View

Janke C, Bulinski J . Post-translational regulation of the microtubule cytoskeleton: mechanisms and functions. Nat Rev Mol Cell Biol. 2011; 12(12):773-86. DOI: 10.1038/nrm3227. View

Coombes C, Yamamoto A, McClellan M, Reid T, Plooster M, Luxton G . Mechanism of microtubule lumen entry for the α-tubulin acetyltransferase enzyme αTAT1. Proc Natl Acad Sci U S A. 2016; 113(46):E7176-E7184. PMC: 5135325. DOI: 10.1073/pnas.1605397113. View

Eden E, Navon R, Steinfeld I, Lipson D, Yakhini Z . GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinformatics. 2009; 10:48. PMC: 2644678. DOI: 10.1186/1471-2105-10-48. View

Borner G, Harbour M, Hester S, Lilley K, Robinson M . Comparative proteomics of clathrin-coated vesicles. J Cell Biol. 2006; 175(4):571-8. PMC: 2064594. DOI: 10.1083/jcb.200607164. View

Kim G, Li L, Ghorbani M, You L, Yang X . Mice lacking α-tubulin acetyltransferase 1 are viable but display α-tubulin acetylation deficiency and dentate gyrus distortion. J Biol Chem. 2013; 288(28):20334-50. PMC: 3711300. DOI: 10.1074/jbc.M113.464792. View

Hinckelmann M, Zala D, Saudou F . Releasing the brake: restoring fast axonal transport in neurodegenerative disorders. Trends Cell Biol. 2013; 23(12):634-43. DOI: 10.1016/j.tcb.2013.08.007. View

Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A . HDAC6 is a microtubule-associated deacetylase. Nature. 2002; 417(6887):455-8. DOI: 10.1038/417455a. View

Butler K, Kalin J, Brochier C, Vistoli G, Langley B, Kozikowski A . Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A. J Am Chem Soc. 2010; 132(31):10842-6. PMC: 2916045. DOI: 10.1021/ja102758v. View

10.

Bicek A, Tuzel E, Demtchouk A, Uppalapati M, Hancock W, Kroll D . Anterograde microtubule transport drives microtubule bending in LLC-PK1 epithelial cells. Mol Biol Cell. 2009; 20(12):2943-53. PMC: 2695801. DOI: 10.1091/mbc.e08-09-0909. View

11.

Song Y, Brady S . Post-translational modifications of tubulin: pathways to functional diversity of microtubules. Trends Cell Biol. 2014; 25(3):125-36. PMC: 4344850. DOI: 10.1016/j.tcb.2014.10.004. View

12.

Reed N, Cai D, Blasius T, Jih G, Meyhofer E, Gaertig J . Microtubule acetylation promotes kinesin-1 binding and transport. Curr Biol. 2006; 16(21):2166-72. DOI: 10.1016/j.cub.2006.09.014. View

13.

Nichols C, Becnel J, Pandey U . Methods to assay Drosophila behavior. J Vis Exp. 2012; (61). PMC: 3671839. DOI: 10.3791/3795. View

14.

Zala D, Hinckelmann M, Yu H, Cunha M, Liot G, Cordelieres F . Vesicular glycolysis provides on-board energy for fast axonal transport. Cell. 2013; 152(3):479-91. DOI: 10.1016/j.cell.2012.12.029. View

15.

Godena V, Brookes-Hocking N, Moller A, Shaw G, Oswald M, Sancho R . Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations. Nat Commun. 2014; 5:5245. PMC: 4208097. DOI: 10.1038/ncomms6245. View

16.

Tsai J, Chen Y, Kriegstein A, Vallee R . LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages. J Cell Biol. 2005; 170(6):935-45. PMC: 2171430. DOI: 10.1083/jcb.200505166. View

17.

Morelli G, Avila A, Ravanidis S, Aourz N, Neve R, Smolders I . Cerebral Cortical Circuitry Formation Requires Functional Glycine Receptors. Cereb Cortex. 2016; 27(3):1863-1877. DOI: 10.1093/cercor/bhw025. View

18.

Howes S, Alushin G, Shida T, Nachury M, Nogales E . Effects of tubulin acetylation and tubulin acetyltransferase binding on microtubule structure. Mol Biol Cell. 2013; 25(2):257-66. PMC: 3890346. DOI: 10.1091/mbc.E13-07-0387. View

19.

Shaver S, Riedl C, Parkes T, Sokolowski M, Hilliker A . Isolation of larval behavioral mutants in Drosophila melanogaster. J Neurogenet. 2001; 14(4):193-205. DOI: 10.3109/01677060009084498. View

20.

Dompierre J, Godin J, Charrin B, Cordelieres F, King S, Humbert S . Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington's disease by increasing tubulin acetylation. J Neurosci. 2007; 27(13):3571-83. PMC: 6672116. DOI: 10.1523/JNEUROSCI.0037-07.2007. View