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

doi:10.1038/s41467-021-25786-y

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

Research output: Contribution to journal › Article › peer-review

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 language	English
Article number	5878
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-25786-y
State	Published - 7 Oct 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2021, The Author(s).

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Access to Document

10.1038/s41467-021-25786-y

Cite this

Even, A., Morelli, G., Turchetto, S., Shilian, M., Bail, R. L., Laguesse, S., Krusy, N., Brisker, A., Brandis, A., Inbar, S., Chariot, A., Saudou, F., Dietrich, P., Dragatsis, I., Brone, B., Broix, L., Rigo, J. M., Weil, M., & Nguyen, L. (2021). ATP-citrate lyase promotes axonal transport across species. Nature Communications, 12(1), Article 5878. https://doi.org/10.1038/s41467-021-25786-y

@article{3195cc2d83fa4dc3bd2f02e3cc2cc344,

title = "ATP-citrate lyase promotes axonal transport across species",

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.",

author = "Aviel Even and Giovanni Morelli and Silvia Turchetto and Michal Shilian and Bail, {Romain Le} and Sophie Laguesse and Nathalie Krusy and Ariel Brisker and Alexander Brandis and Shani Inbar and Alain Chariot and Fr{\'e}d{\'e}ric Saudou and Paula Dietrich and Ioannis Dragatsis and Bert Brone and Lo{\"i}c Broix and Rigo, {Jean Michel} and Miguel Weil and Laurent Nguyen",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = oct,

day = "7",

doi = "10.1038/s41467-021-25786-y",

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

TY - JOUR

T1 - ATP-citrate lyase promotes axonal transport across species

AU - Even, Aviel

AU - Morelli, Giovanni

AU - Turchetto, Silvia

AU - Shilian, Michal

AU - Bail, Romain Le

AU - Laguesse, Sophie

AU - Krusy, Nathalie

AU - Brisker, Ariel

AU - Brandis, Alexander

AU - Inbar, Shani

AU - Chariot, Alain

AU - Saudou, Frédéric

AU - Dietrich, Paula

AU - Dragatsis, Ioannis

AU - Brone, Bert

AU - Broix, Loïc

AU - Rigo, Jean Michel

AU - Weil, Miguel

AU - Nguyen, Laurent

PY - 2021/10/7

Y1 - 2021/10/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85116539153&partnerID=8YFLogxK

U2 - 10.1038/s41467-021-25786-y

DO - 10.1038/s41467-021-25786-y

M3 - Article

C2 - 34620845

AN - SCOPUS:85116539153

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5878

ER -

ATP-citrate lyase promotes axonal transport across species

Abstract

Bibliographical note

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this