ATAT1-enriched vesicles promote microtubule acetylation via axonal transport

Aviel Even, Giovanni Morelli, Loïc 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, Frédéric Saudou, Miguel Weil, Laurent Nguyen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbereaax2705
JournalScience advances
Volume5
Issue number12
DOIs
StatePublished - 18 Dec 2019

Funding

FundersFunder number
Columbia University, New York
EMBO LTFALTF 693-2015
Ela Kodesz Institute
Fondation Médicale Reine Elisabeth
Fondation Simone et Pierre Clerdent
IAP-VII network P7/10
IAP-VII network P7/20
Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science
NeuroTalk
European Molecular Biology OrganizationASTF 174-2016
Horizon 2020 Framework ProgrammeFDT201904008210, 675737
Fondation Vaincre AlzheimerFR-16055p
Agence Nationale de la RechercheANR-15-JPWG-0003-05 JPND CIRCPROT, ANR-10-IDEX-0001-02, ANR-11-LBX-003, ANR-15-IDEX-02 NeuroCoG, ANR-14-CE35-0027-01, ANR-17-CE13-0021
Belgian Federal Science Policy Office
Fondation pour la Recherche MédicaleDEQ20170336756
Israel Science Foundation1688/16
Tel Aviv University
Université de Liège
Fonds Léon Fredericq
Institut Curie

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