Publications of Laurent Nguyen
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See detailATP-citrate lyase promotes axonal transport across species.
Even, Aviel; Morelli, Giovanni ULiege; Turchetto, Silvia ULiege et al

in Nature Communications (2021), 12(1), 5878

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 ... [more ▼]

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. [less ▲]

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See detailUnveiling the alcohol-dependent alterations of local translation in the prefrontal cortex during adolescence
Van Hees, Laura ULiege; Nguyen, Laurent ULiege; Laguesse, Sophie ULiege

Poster (2019, September)

Alcohol use disorder (AUD) is a devastating relapsing disease which represents the fourth leading cause of preventable death worldwide. The neural mechanisms of AUD have remained uncertain, and multiple ... [more ▼]

Alcohol use disorder (AUD) is a devastating relapsing disease which represents the fourth leading cause of preventable death worldwide. The neural mechanisms of AUD have remained uncertain, and multiple genetic, psychological and environmental factors are thought to be involved. AUD has mainly been considered as a pathological condition in adults, but recent evidence suggests that the roots of alcohol addiction begin to grow during adolescence. Adolescence is a critical developmental period characterized by significant changes in brain architecture and behaviors. Brain maturation begins in posterior regions and progresses towards anterior higher-order regions, including the prefrontal cortex (PFC). The PFC is implicated in executive functions and its immaturity in adolescents is associated with lack of inhibitory control over behavior, increased impulsivity and desire of risk-taking. It is widely believed that the enhanced ability of the adolescent PFC to undergo experience-dependent changes is associated with heightened vulnerability to exogenous agents, including alcohol. According to the National Institute on Alcohol Abuse and Alcoholism (NIAAA), alcohol is the most consumed drug among adolescents, with 40% reporting regularly experiencing binge-drinking episodes. This pattern of alcohol consumption is particularly harmful as it may interfere with the ongoing maturation of frontal brain circuits, leading to profound long-lasting consequences on PFC structure and function. In particular, the adolescent PFC shows structural and molecular alterations with alcohol exposure such as reduced thickness and activity, neuroimmune genes induction, loss of cholinergic neurons, aberrant dendritic spine density, and alteration of dopamine neurotransmission. In addition, adolescent alcohol exposure (AAE) is related to serious psychological problems, comorbid psychopathology and detrimental neurocognitive consequences, and clinical studies have shown that AAE significantly increases the risk of developing psychiatric and behavioral disorders later in life, including addiction. Accordingly, animal studies have reported that AAE leads to impaired PFC function associated with defective behaviors. However, the precise cellular mechanisms underlying the alcohol-induced cognitive and behavioral impairments, the molecular mechanisms underlying defects in PFC maturation, and possible sex differences are still poorly understood. Alcohol addiction is considered as a maladaptive form of learning and memory. Indeed, alcohol is thought to “usurp” the molecular mechanisms underlying those processes, including synaptic plasticity, which depends on the local translation of mRNAs at synaptic sites. It has recently been shown in adult mice that excessive alcohol consumption modifies synaptic protein composition in brain regions associated with the mesocorticolimbic pathway, promoting the development and maintenance of addiction. The mammalian target of rapamycin complex 1 (mTORC1) and the eukaryotic initiation factor 2α (eIF2α) are master regulators of local translation. We previously reported that alcohol binge-drinking in adult mice activates mTORC1 signaling in key striatal and cortical areas, enhancing synaptic protein translation and inducing neuroadaptations that in turn promote alcohol seeking and taking. Moreover, mTORC1 in the PFC is required for the retrieval of alcohol-associated memories, and has been associated with PFC development, connectivity and related behaviors. In parallel, eIF2α has been shown to regulate synaptic plasticity underlying memory and addiction, and has also been implicated in PFC function. However, the alcohol-dependent modulation of mTORC1 and eIF2α activity in the maturating PFC and the alcohol-induced defects in local translation have remained unknown. The specific aims of this project are (1) to determine whether AAE perturbs the maturation of the PFC and induces structural, physiological and/or behavioral defects; (2) to reveal whether alcohol modulates local dendritic translation via mTORC1 and/or eIF2α and leads to defective synaptic plasticity in the adolescent PFC; (3) to study the AAE-induced local translation alterations in specific neuronal subtypes and identify mRNA candidates. This work aims to provide new insight on the molecular mechanisms underlying alcohol’s actions in the maturating PFC by focusing on local translation. By using a mouse model of voluntary adolescent binge drinking, we showed that excessive alcohol consumption during adolescence leads to long-lasting behavioral impairments in adulthood, such as increased anxiety and alcohol intake, as well as reduced cognitive performances. We also report that AAE increases mTORC1 signaling in the PFC of adolescent mice. By using transgenic mouse lines and Ribotag profiling, we are comparing the synaptic translatome of specific neuronal populations in the PFC (i.e. glutamatergic neurons and interneurons) in order to identify candidate synaptic mRNAs whose translation levels are modified by AAE. [less ▲]

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See detailL’expérimentation animale : toujours une nécessité pour la santé animale et humaine
Balthazart, Jacques ULiege; Blanpain, Cédric; Bureau, Fabrice ULiege et al

Article for general public (2019)

Le 1 juillet 2019, « Le Soir » publiait un article relatant la découverte par les chercheurs de l'UCLouvain d'une bactérie pouvant potentiellement contribuer à limiter les risques cardiovasculaires , l ... [more ▼]

Le 1 juillet 2019, « Le Soir » publiait un article relatant la découverte par les chercheurs de l'UCLouvain d'une bactérie pouvant potentiellement contribuer à limiter les risques cardiovasculaires , l'une des premières causes de décès en Belgique. Cet article soulignait l'importance de la recherche fondamentales et du passage nécessaire par l'expérimentation préclinique (animale) pour développer une application chez l’humain. En réaction, Solange T'Kint, administratrice de l'ASBL S.E.A. - Suppression des Expériences sur l'Animal-, publiait le 2 juillet dans « La Libre » un nouveau pamphlet contre l'expérimentation animale. Mme T Kint avait déjà lancé en aout 2018 une pétition attaquant la découverte3 d'un chercheur de l'ULB sur la dépendance aux drogues réalisée chez la souris , démontrant par là à quel point toute avancée médicale imputable à l'expérimentation animale lui est insupportable. Ici se trouve la réponse de Scientifiques qui pensent indispensable d’informer chacun-e- de manière rigoureuse et de ne jamais laisser diffuser de « fake news » sans réagir. [less ▲]

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See detailCell migration promotes dynamic cellular interactions to control cerebral cortex morphogenesis.
Gomes Da Silva, Carla ULiege; Peyre, Elise; Nguyen, Laurent ULiege

in Nature Reviews. Neuroscience (2019)

The cerebral cortex is an evolutionarily advanced brain structure that computes higher motor, sensory and cognitive functions. Its complex organization reflects the exquisite cell migration and ... [more ▼]

The cerebral cortex is an evolutionarily advanced brain structure that computes higher motor, sensory and cognitive functions. Its complex organization reflects the exquisite cell migration and differentiation patterns that take place during embryogenesis. Recent evidence supports an essential role for cell migration in shaping the developing cerebral cortex via direct cellular contacts and spatially organized diffusible cues that regulate the establishment of its cytoarchitecture and function. Identifying the nature of the crosstalk between cell populations at play during brain development is key to understanding how cerebral cortical morphogenesis proceeds in health and disease. [less ▲]

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See detailTemporal patterning of apical progenitors and their daughter neurons in the developing neocortex.
Telley, L.; Agirman, Gulistan ULiege; Prados, J. et al

in Science (2019), 364(6440),

During corticogenesis, distinct subtypes of neurons are sequentially born from ventricular zone progenitors. How these cells are molecularly temporally patterned is poorly understood. We used single-cell ... [more ▼]

During corticogenesis, distinct subtypes of neurons are sequentially born from ventricular zone progenitors. How these cells are molecularly temporally patterned is poorly understood. We used single-cell RNA sequencing at high temporal resolution to trace the lineage of the molecular identities of successive generations of apical progenitors (APs) and their daughter neurons in mouse embryos. We identified a core set of evolutionarily conserved, temporally patterned genes that drive APs from internally driven to more exteroceptive states. We found that the Polycomb repressor complex 2 (PRC2) epigenetically regulates AP temporal progression. Embryonic age-dependent AP molecular states are transmitted to their progeny as successive ground states, onto which essentially conserved early postmitotic differentiation programs are applied, and are complemented by later-occurring environment-dependent signals. Thus, epigenetically regulated temporal molecular birthmarks present in progenitors act in their postmitotic progeny to seed adult neuronal diversity. [less ▲]

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See detailATAT1-enriched vesicles promote microtubule acetylation via axonal transport.
Even, Aviel; Morelli, Giovanni ULiege; Broix, Loïc ULiege et al

in Science Advances (2019), 5(12), 2705

Microtubules are polymerized dimers of alpha- and beta-tubulin that underlie a broad range of cellular activities. Acetylation of alpha-tubulin by the acetyltransferase ATAT1 modulates microtubule ... [more ▼]

Microtubules are polymerized dimers of alpha- and beta-tubulin that underlie a broad range of cellular activities. Acetylation of alpha-tubulin by the acetyltransferase ATAT1 modulates microtubule dynamics and functions in neurons. However, it remains unclear how this enzyme acetylates microtubules over long distances in axons. Here, we show that loss of ATAT1 impairs axonal transport in neurons in vivo, and cell-free motility assays confirm a requirement of alpha-tubulin acetylation for proper bidirectional vesicular transport. Moreover, we demonstrate that the main cellular pool of ATAT1 is transported at the cytosolic side of neuronal vesicles that are moving along axons. Together, our data suggest that axonal transport of ATAT1-enriched vesicles is the predominant driver of alpha-tubulin acetylation in axons. [less ▲]

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See detailThe centrosome protein AKNA regulates neurogenesis via microtubule organization
Camargo Ortega, G.; Falk, S.; Johansson, P. A. et al

in Nature (2019), 567(7746), 113-117

The expansion of brain size is accompanied by a relative enlargement of the subventricular zone during development. Epithelial-like neural stem cells divide in the ventricular zone at the ventricles of ... [more ▼]

The expansion of brain size is accompanied by a relative enlargement of the subventricular zone during development. Epithelial-like neural stem cells divide in the ventricular zone at the ventricles of the embryonic brain, self-renew and generate basal progenitors 1 that delaminate and settle in the subventricular zone in enlarged brain regions 2 . The length of time that cells stay in the subventricular zone is essential for controlling further amplification and fate determination. Here we show that the interphase centrosome protein AKNA has a key role in this process. AKNA localizes at the subdistal appendages of the mother centriole in specific subtypes of neural stem cells, and in almost all basal progenitors. This protein is necessary and sufficient to organize centrosomal microtubules, and promote their nucleation and growth. These features of AKNA are important for mediating the delamination process in the formation of the subventricular zone. Moreover, AKNA regulates the exit from the subventricular zone, which reveals the pivotal role of centrosomal microtubule organization in enabling cells to both enter and remain in the subventricular zone. The epithelial-to-mesenchymal transition is also regulated by AKNA in other epithelial cells, demonstrating its general importance for the control of cell delamination. © 2019, The Author(s), under exclusive licence to Springer Nature Limited. [less ▲]

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See detailExpérimentation animale: la recette d'une polémique scientifique
Muraille, Eric; de kerchove, Alban; Muylkens, Benoit et al

Article for general public (2018)

La majorité du grand public accepte l’expérimentation animale à condition que celle-ci contribue à l’amélioration de la santé humaine et qu’aucune autre alternative n’existe. En face, les opposants ... [more ▼]

La majorité du grand public accepte l’expérimentation animale à condition que celle-ci contribue à l’amélioration de la santé humaine et qu’aucune autre alternative n’existe. En face, les opposants décrédibilisent la recherche et stigmatise une profession à des fins idéologiques. Relevé de leurs arguments. [less ▲]

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See detailp27Kip1 Modulates Axonal Transport by Regulating α-Tubulin Acetyltransferase 1 Stability
Morelli, Giovanni ULiege; Even, Aviel; Gladwyn-Ng, Ivan ULiege et al

Poster (2018, June 08)

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See detailLa souris, le patient, et le faux expert. Décryptage d'une mystification.
Bakker, Julie ULiege; Balthazart, Jacques ULiege; Baron, Frédéric ULiege et al

Article for general public (2018)

La recherche sur animaux est actuellement encadrée de façon stricte en Wallonie comme dans toute l'Union Européenne (voir l'article de Marc Vandenheede publié dans le Vif). Cette législation et les ... [more ▼]

La recherche sur animaux est actuellement encadrée de façon stricte en Wallonie comme dans toute l'Union Européenne (voir l'article de Marc Vandenheede publié dans le Vif). Cette législation et les contrôles qui y sont associés induisent de nombreuses contraintes pratiques, des charges administratives et des coûts financiers importants que les chercheurs seraient certainement heureux d'éviter s'il existait une alternative à l'expérimentation animale. [less ▲]

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See detailAnalyse détaillée de la seconde version de l’avant-projet de Code du bien-être animal wallon. Lecture commentée au 21/03/2018 du Chapitre 8 (Expérimentation animale)
Drion, Pierre ULiege; Corhay, Albert ULiege; Haubruge, Eric ULiege et al

Report (2018)

La compétence « bien-être animal », auparavant fédérale, a été régionalisée en juillet 2014. Ce projet de code vise à remplacer les dispositions légales en vigueur (la Loi de 1984 telle que modifiée par ... [more ▼]

La compétence « bien-être animal », auparavant fédérale, a été régionalisée en juillet 2014. Ce projet de code vise à remplacer les dispositions légales en vigueur (la Loi de 1984 telle que modifiée par les décrets du Gouvernement wallon). Certains éléments sont repris tels quels de la Directive 2010/63. Cela est nécessaire car la Directive européenne en tant que telle n’a pas de force obligatoire en Belgique. Elle doit être transcrite par un instrument législatif (avant, la Loi de 1984 et ses modifications, aujourd’hui, le projet de code pour la Région wallonne). Certains aspects semblent flous, mais renvoient à des dispositions que le Gouvernement doit encore prendre (au travers d’arrêtés du Gouvernement wallon, comme le faisaient avant les nombreux arrêtés royaux et du gouvernement qui réglementent la matière). Les arrêtés d’exécution devront obligatoirement tenir compte de la Directive européenne et s’inspirer de dispositions actuellement en vigueur. [less ▲]

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See detailLessons learnt from the emergence of Zika virus
Lecuit, Marc; Nguyen, Laurent ULiege

in Nature Microbiology (2018), 3(9), 966-968

Looking back at how Zika virus emergence was handled during and after the 2015–2016 outbreak will be important for assessing how well multiple relevant stakeholders were integrated to mount a response ... [more ▼]

Looking back at how Zika virus emergence was handled during and after the 2015–2016 outbreak will be important for assessing how well multiple relevant stakeholders were integrated to mount a response, and can provide the groundwork to better cope with emerging infections in the future. © 2018, The Author(s). [less ▲]

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See detailImportin-8 Modulates Division of Apical Progenitors, Dendritogenesis and Tangential Migration During Development of Mouse Cortex.
Nganou, Gerry; Gomes Da Silva, Carla ULiege; Gladwyn-Ng, Ivan ULiege et al

in Frontiers in Molecular Neuroscience (2018), 11

The building of the brain is a multistep process that requires the coordinate expression of thousands of genes and an intense nucleocytoplasmic transport of RNA and proteins. This transport is mediated by ... [more ▼]

The building of the brain is a multistep process that requires the coordinate expression of thousands of genes and an intense nucleocytoplasmic transport of RNA and proteins. This transport is mediated by karyopherins that comprise importins and exportins. Here, we investigated the role of the ss-importin, importin-8 (IPO8) during mouse cerebral corticogenesis as several of its cargoes have been shown to be essential during this process. First, we showed that Ipo8 mRNA is expressed in mouse brain at various embryonic ages with a clear signal in the sub-ventricular/ventricular zone (SVZ/VZ), the cerebral cortical plate (CP) and the ganglionic eminences. We found that acute knockdown of IPO8 in cortical progenitors reduced both their proliferation and cell cycle exit leading to the increase in apical progenitor pool without influencing the number of basal progenitors (BPs). Projection neurons ultimately reached their appropriate cerebral cortical layer, but their dendritogenesis was specifically affected, resulting in neurons with reduced dendrite complexity. IPO8 knockdown also slowed the migration of cortical interneurons. Together, our data demonstrate that IPO8 contribute to the coordination of several critical steps of cerebral cortex development. These results suggest that the impairment of IPO8 function might be associated with some diseases of neuronal migration defects. [less ▲]

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See detailA yellow fever–Zika chimeric virus vaccine candidate protects against Zika infection and congenital malformations in mice
Kum, D. B.; Mishra, N.; Boudewijns, R. et al

in npj Vaccines (2018), 3(1),

The recent Zika virus (ZIKV) epidemic in the Americas led to an intense search for therapeutics and vaccines. Here we report the engineering of a chimeric virus vaccine candidate (YF-ZIKprM/E) by ... [more ▼]

The recent Zika virus (ZIKV) epidemic in the Americas led to an intense search for therapeutics and vaccines. Here we report the engineering of a chimeric virus vaccine candidate (YF-ZIKprM/E) by replacing the antigenic surface glycoproteins and the capsid anchor of YFV-17D with those of a prototypic Asian lineage ZIKV isolate. By intracellular passaging, a variant with adaptive mutations in the E protein was obtained. Unlike YFV-17D, YF-ZIKprM/E replicates poorly in mosquito cells. Also, YF-ZIKprM/E does not cause disease nor mortality in interferon α/β, and γ receptor KO AG129 mice nor following intracranial inoculation of BALB/c pups. A single dose as low as 1 × 10 2 PFU results, as early as 7 days post vaccination, in seroconversion to neutralizing antibodies and confers full protection in AG129 mice against stringent challenge with a lethal inoculum (10 5 LD 50 ) of either homologous or heterologous ZIKV strains. Induction of multi-functional CD4 + and CD8 + T cell responses against ZIKV structural and YFV-17D non-structural proteins indicates that cellular immunity may also contribute to protection. Vaccine immunogenicity and protection was confirmed in other mouse strains, including after temporal blockade of interferon-receptors in wild-type mice to facilitate ZIKV replication. Vaccination of wild-type NMRI dams with YF-ZIKprM/E results in complete protection of foetuses against brain infections and malformations following a stringent intraplacental challenge with an epidemic ZIKV strain. The particular characteristic of YF-ZIKprM/E in terms of efficacy and its marked attenuation in mice warrants further exploration as a vaccine candidate. © 2018, The Author(s). [less ▲]

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See detailElongator subunit 3 (ELP3) modifies ALS through tRNA modification
Bento-Abreu, A.; Jager, G.; Swinnen, B. et al

in Human Molecular Genetics (2018), 27(7), 1276-1289

Amyotrophic lateral sclerosis (ALS) is a fatal degenerative motor neuron disorder of which the progression is influenced by several disease-modifying factors. Here, we investigated ELP3, a subunit of the ... [more ▼]

Amyotrophic lateral sclerosis (ALS) is a fatal degenerative motor neuron disorder of which the progression is influenced by several disease-modifying factors. Here, we investigated ELP3, a subunit of the elongator complex that modifies tRNA wobble uridines, as one of such ALS disease modifiers. ELP3 attenuated the axonopathy of a mutant SOD1, as well as of a mutant C9orf72 ALS zebrafish model. Furthermore, the expression of ELP3 in the SOD1G93A mouse extended the survival and attenuated the denervation in this model. Depletion of ELP3 in vitro reduced the modified tRNA wobble uridine mcm5s2U and increased abundance of insoluble mutant SOD1, which was reverted by exogenous ELP3 expression. Interestingly, the expression of ELP3 in the motor cortex of ALS patients was reduced and correlated with mcm5s2U levels. Our results demonstrate that ELP3 is a modifier of ALS and suggest a link between tRNA modification and neurodegeneration. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. [less ▲]

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See detailCerebral cortex development: an outside-in perspective.
Agirman, Gulistan ULiege; Broix, Loic; Nguyen, Laurent ULiege

in FEBS Letters (2017), 591(24), 3978-3992

The cerebral cortex is a complex structure that contains different classes of neurons distributed within six layers and regionally organized into highly specialized areas. Cortical layering arises during ... [more ▼]

The cerebral cortex is a complex structure that contains different classes of neurons distributed within six layers and regionally organized into highly specialized areas. Cortical layering arises during embryonic development in an inside-out manner as forebrain progenitors proliferate and generate distinct waves of interneurons and projection neurons. Radial glial cells (RGCs) derive from neuroepithelial cells and are the founding cortical progenitors. At the onset of corticogenesis, RGCs expand their pool by proliferative divisions. As corticogenesis proceeds, they gradually undergo differentiative divisions to either generate neurons directly (direct neurogenesis) or indirectly via production of intermediate progenitors that further divide to generate pairs of neurons (indirect neurogenesis). The fate of RGCs is finely regulated during all the corticogenesis process and depends on time-scaled perception of external signals and expression of intrinsic factors. The present Review focuses on the role of physiological extracellular cues arising from the vicinity of neural progenitors on the regulation of dorsal neurogenesis and cerebral cortex patterning. It further discusses how pathogenic viral factors influence RGC behaviour and disrupt cerebral cortex development. [less ▲]

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See detailLoss of Elp3 Impairs the Acetylation and Distribution of Connexin-43 in the Developing Cerebral Cortex.
Laguesse, Sophie ULiege; Close, Pierre ULiege; Van Hees, Laura ULiege et al

in Frontiers in Cellular Neuroscience (2017), 11

The Elongator complex is required for proper development of the cerebral cortex. Interfering with its activity in vivo delays the migration of postmitotic projection neurons, at least through a defective ... [more ▼]

The Elongator complex is required for proper development of the cerebral cortex. Interfering with its activity in vivo delays the migration of postmitotic projection neurons, at least through a defective alpha-tubulin acetylation. However, this complex is already expressed by cortical progenitors where it may regulate the early steps of migration by targeting additional proteins. Here we report that connexin-43 (Cx43), which is strongly expressed by cortical progenitors and whose depletion impairs projection neuron migration, requires Elongator expression for its proper acetylation. Indeed, we show that Cx43 acetylation is reduced in the cortex of Elp3cKO embryos, as well as in a neuroblastoma cell line depleted of Elp1 expression, suggesting that Cx43 acetylation requires Elongator in different cellular contexts. Moreover, we show that histones deacetylase 6 (HDAC6) is a deacetylase of Cx43. Finally, we report that acetylation of Cx43 regulates its membrane distribution in apical progenitors of the cerebral cortex. [less ▲]

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See detailELP3 links tRNA modification to IRES-dependent translation of LEF-1 to promote metastasis in breast cancer
Delaunay, Sylvain ULiege; Rapino, Francesca ULiege; Tharun, Lars et al

in Journal of Experimental Medicine (2016), 213

Quantitative and qualitative changes in mRNA translation occur in tumor cells and support cancer progression and metastasis. Post-transcriptional nucleoside modifications of transfer RNAs (tRNAs) at the ... [more ▼]

Quantitative and qualitative changes in mRNA translation occur in tumor cells and support cancer progression and metastasis. Post-transcriptional nucleoside modifications of transfer RNAs (tRNAs) at the wobble U34 base are highly conserved and contribute to translation fidelity. Here, we show that ELP3 and CTU1/2, partner enzymes in U34 mcm5s2-tRNA modification, are upregulated in human breast cancers and sustain metastasis. Elp3 genetic ablation strongly impaired invasion and metastasis formation in the PyMT model of invasive breast cancer. Mechanistically, ELP3 and CTU1/2 support cellular invasion through the translation of the oncoprotein DEK. As a result, DEK promotes the IRES-dependent translation of the pro-invasive transcription factor LEF1. Consistently, a DEK mutant, whose codon composition is independent of U34 mcm5s2-tRNA modification, escapes the ELP3- and CTU1-dependent regulation and restores the IRES-dependent LEF1 expression. Our results demonstrate the key role of U34 tRNA modification to support specific translation during breast cancer progression and highlight a functional link between tRNA modification- and IRES-dependent translation during tumor cell invasion and metastasis. [less ▲]

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