ATP-citrate lyase promotes axonal transport across species

Aviel Even, Giovanni Morelli, Silvia Turchetto, Michal Shilian, Romain Le Bail, Sophie Laguesse, Nathalie Krusy, Ariel Brisker, Alexander Brandis, Shani Inbar, Alain Chariot, Frédéric Saudou, Paula Dietrich, Ioannis Dragatsis, Bert Brone, Loïc Broix, Jean Michel Rigo, Miguel Weil*, Laurent Nguyen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Microtubule (MT)-based transport is an evolutionary conserved process finely tuned by posttranslational modifications. Among them, α-tubulin acetylation, primarily catalyzed by a vesicular pool of α-tubulin N-acetyltransferase 1 (Atat1), promotes the recruitment and processivity of molecular motors along MT tracks. However, the mechanism that controls Atat1 activity remains poorly understood. Here, we show that ATP-citrate lyase (Acly) is enriched in vesicles and provide Acetyl-Coenzyme-A (Acetyl-CoA) to Atat1. In addition, we showed that Acly expression is reduced upon loss of Elongator activity, further connecting Elongator to Atat1 in a pathway regulating α-tubulin acetylation and MT-dependent transport in projection neurons, across species. Remarkably, comparable defects occur in fibroblasts from Familial Dysautonomia (FD) patients bearing an autosomal recessive mutation in the gene coding for the Elongator subunit ELP1. Our data may thus shine light on the pathophysiological mechanisms underlying FD.

Original languageEnglish
Article number5878
JournalNature Communications
Volume12
Issue number1
DOIs
StatePublished - 1 Dec 2021

Funding

FundersFunder number
F.R.S.-F.N.R.S.
Fondation Médicale Reine Elisabeth
Fondation Simone et Pierre Clerdent
IAP-VII network P7/20
NeuroTalk
European Molecular Biology OrganizationASTF 174-2016
Agence Nationale de la RechercheANR-18-CE16-0009-01 AXYON, ANR-15-IDEX-02 NeuroCoG
Fonds De La Recherche Scientifique - FNRSEOS 0019118F-RG36
Belgian Federal Science Policy Office
Fondation pour la Recherche MédicaleDEI20151234418
Israel Science Foundation1688/16
Fonds Léon Fredericq

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