Nature communications, 2021-10, Vol.12 (1), p.5878-5878, Article 5878
2021
Details
- Autor(en) / Beteiligte
- Titel
- ATP-citrate lyase promotes axonal transport across species
- Ist Teil von
- Nature communications, 2021-10, Vol.12 (1), p.5878-5878, Article 5878
- Ort / Verlag
- London: Nature Publishing Group
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-021-25786-yTitel-ID: cdi_doaj_primary_oai_doaj_org_article_56060abcde1a4c4f802c73b700424575
- Format
- –
- Schlagworte
- Acetyl Coenzyme A/metabolism, Acetylation, Acetyltransferase, Acetyltransferases/genetics, Animals, ATP, ATP Citrate (pro-S)-Lyase/genetics/metabolism, ATP citrate lyase, Axonal transport, Axonal Transport/genetics/physiology, Axons, Drosophila melanogaster, Dysautonomia, Dysautonomia, Familial/metabolism, Elongation, Evolutionary conservation, Female, Fibroblasts, Fibroblasts/metabolism, Human health sciences, Humans, Interdisciplinary aspects, Laboratories, Larva, Life sciences, Male, Medical research, Mice, Microtubules/metabolism, Mitochondria, Molecular motors, Mutation, N-acetyltransferase 1, Neural coding, Neurological disorders, Neurologie, Neurology, Neurosciences, Protein Processing, Post-Translational, Proteins, Sciences de la santé humaine, Stem cells, Tracks (paths), Tubulin, Tubulin N-acetyltransferase, Tubulin/metabolism