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Title: | ATP-citrate lyase promotes axonal transport across species | Authors: | EVEN, Aviel MORELLI, Giovanni Turchetto, Silvia Shilian, Michal Le Bail, Romain Laguesse, Sophie Krusy, Nathalie Brisker, Ariel Brandis, Alexander Inbar, Shani Chariot, Alain Saudou, Frederic Dietrich, Paula Dragatsis, Ioannis Weil, Miguel BRONE, Bert Broix, Loic RIGO, Jean-Michel Nguyen, Laurent |
Issue Date: | 2021 | Publisher: | NATURE PORTFOLIO | Source: | NATURE COMMUNICATIONS, 12 (1) (Art N° 5878) | Abstract: | Microtubule (MT)-based transport is an evolutionary conserved process finely tuned by posttranslational modifications. Among them, alpha-tubulin acetylation, primarily catalyzed by a vesicular pool of alpha-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 alpha-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. Microtubule tracks are important for the transport of molecules within axons. Here, the authors show that ATAT1, the enzyme responsible for acetylating a-tubulin, receives acetyl groups from ATP citrate lyase whose stability is regulated by Elongator, a protein mutated in the neuronal disease Familial dysautonomia. | Notes: | Weil, M (corresponding author), Tel Aviv Univ, George S Wise Fac Life Sci, Shmunis Sch Biomed & Canc Res, Sagol Sch Neurosci,Lab Neurodegenerat Dis & Perso, IL-69978 Ramat Aviv, Israel.; Nguyen, L (corresponding author), Univ Liege, CHU Sart Tilman, Interdisciplinary Cluster Appl Genoprote GIGA R, Lab Mol Regulat Neurogenesis,GIGA Stem Cells, B-4000 Liege, Belgium. miguelw@tauex.tau.ac.il; lnguyen@uliege.be |
Keywords: | ATP Citrate (pro-S)-Lyase;Acetyl Coenzyme A;Acetylation;Acetyltransferases;Animals;Axonal Transport;Drosophila melanogaster;Dysautonomia, Familial;Female;Fibroblasts;Humans;Larva;Male;Mice;Microtubules;Protein Processing, Post-Translational;Tubulin | Document URI: | http://hdl.handle.net/1942/35943 | e-ISSN: | 2041-1723 | DOI: | 10.1038/s41467-021-25786-y | ISI #: | WOS:000704983300015 | Rights: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2023 |
Appears in Collections: | Research publications |
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ATP-citrate.pdf | Published version | 0 B | Adobe PDF | View/Open |
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