ATP-citrate lyase promotes axonal transport across species.

ATP Citrate (pro-S)-Lyase/genetics/metabolism; Acetyl Coenzyme A/metabolism; Acetylation; Acetyltransferases/genetics; Animals; Axonal Transport/genetics/physiology; Drosophila melanogaster; Dysautonomia, Familial/metabolism; Female; Fibroblasts/metabolism; Humans; Larva; Male; Mice; Microtubules/metabolism; Protein Processing, Post-Translational; Tubulin/metabolism

Abstract :

[en] 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.

Disciplines :

Neurology

Author, co-author :

Even, Aviel ^✱

Morelli, Giovanni ^✱

Turchetto, Silvia ^✱; Université de Liège - ULiège > GIGA Stem Cells - Molecular Regulation of Neurogenesis

Shilian, Michal

Le Bail, Romain

Laguesse, Sophie ; Université de Liège - ULiège > GIGA Stem Cells - Molecular Regulation of Neurogenesis

Krusy, Nathalie

Brisker, Ariel

Brandis, Alexander

Inbar, Shani

More authors (9 more)

^✱ These authors have contributed equally to this work.

Language :

English

Title :

ATP-citrate lyase promotes axonal transport across species.

Publication date :

2021

Journal title :

Nature Communications

eISSN :

2041-1723

Publisher :

Nature Publishing Group, United Kingdom

Volume :

Issue :

Pages :

5878

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBi :

since 03 November 2021

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