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Publication

ATP-citrate lyase promotes axonal transport across species

Journal Contribution - Journal Article

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.
Journal: Nature communications
ISSN: 2041-1723
Issue: 1
Volume: 12
Publication year:2021
BOF-keylabel:yes
IOF-keylabel:yes
BOF-publication weight:6
Authors:International
Authors from:Higher Education
Accessibility:Open