Physiological and pathological functions of TMEM106B: a gene associated with brain aging and multiple brain disorders

Feng, Tuancheng; Lacrampe, Alexander; Hu, Fenghua

doi:10.1007/s00401-020-02246-3

Cited by 62 publications

(90 citation statements)

References 90 publications

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“…During exit, SARS-CoV-2 progeny virions may first travel from the SMV to the Golgi intermediate compartments and subsequently re-routed to a deacidified lysosomal compartment before getting released from host cells. A few host factors that are known to regulate lysosomal trafficking, such as RAB7A (a RAS-related GTP-binding protein that regulates endo-lysosomal trafficking), ADP Ribosylation Factor Like GTPase 8A (ARL8A, a regulator of lysosome mobility), and TMEM106B (a regulator of lysosomal pH, morphology trafficking, and exocytosis), may play a role in modulating the lysosomal exocytosis process [ 13 • , 16 , 108 •• , 109 ]. Intriguingly, colocalization of SARS-CoV-2 virions on cell surface filopodial protrusions was commonly observed on infected cells, suggesting a strategy for the virus to release or spread from cell to cell [ 80 ].…”

Section: Sars-cov-2 Assembly and Exitmentioning

confidence: 99%

Know your enemy and know yourself – the case of SARS-CoV-2 host factors

Lee

Yousefi

Yan

et al. 2021

Current Opinion in Virology

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Section: Sars-cov-2 Assembly and Exitmentioning

confidence: 99%

Know your enemy and know yourself – the case of SARS-CoV-2 host factors

Lee

Yousefi

Yan

et al. 2021

Current Opinion in Virology

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“…The gene responsible for HLD15, in contrast, is the glutamyl-prolyl-aminoacyl-trna synthetase 1 (eprs1) gene, which encodes the EPRS1 protein, a bifunctional aminoacyl-tRNA synthetase that catalyzes the aminoacylation of glutamic acid and proline tRNA species. HLD15-associated mutation of EPRS1 proteins results in decreased translation capacity, leading to insufficient myelination in the developing brain [9][10][11]. In brain imaging, HLD15 appears as a hypomyelinating leukodystrophy with thin corpus callosum.…”

Section: Introductionmentioning

confidence: 99%

“…In brain imaging, HLD15 appears as a hypomyelinating leukodystrophy with thin corpus callosum. HLDs involving HLD15 are diagnosed with reference to both clinical and magnetic resonance imaging (MRI) features followed by genetic confirmation [9][10][11]. The features of HLD15 include significant visual loss with variable amblyopia and dysphagia as well as dystonia, ataxia, and spasticity, although the severity of the disorder is variable.…”

Section: Introductionmentioning

confidence: 99%

“…Most HLD15 patients develop severe optic atrophy and some have hearing loss [11]. To date, no therapeutic strategy has been established, and symptomatic treatment, such as anticonvulsant medications for patients with spasticity, is the typical response [5][6][7][8][9][10][11]. While HLD15-associated mutations of EPRS1 decrease EPRS protein expression levels [11], some residual mutant proteins remain, yet it is unclear how these mutant proteins cause the disease's molecular and cellular pathological effects.…”

Section: Introductionmentioning

confidence: 99%

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Hypomyelinating Leukodystrophy 15 (HLD15)-Associated Mutation of EPRS1 Leads to Its Polymeric Aggregation in Rab7-Positive Vesicle Structures, Inhibiting Oligodendroglial Cell Morphological Differentiation

et al. 2021

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Pelizaeus–Merzbacher disease (PMD), also known as hypomyelinating leukodystrophy 1 (HLD1), is an X-linked recessive disease affecting in the central nervous system (CNS). The gene responsible for HLD1 encodes proteolipid protein 1 (plp1), which is the major myelin structural protein produced by oligodendroglial cells (oligodendrocytes). HLD15 is an autosomal recessive disease affecting the glutamyl-prolyl-aminoacyl-tRNA synthetase 1 (eprs1) gene, whose product, the EPRS1 protein, is a bifunctional aminoacyl-tRNA synthetase that is localized throughout cell bodies and that catalyzes the aminoacylation of glutamic acid and proline tRNA species. Here, we show that the HLD15-associated nonsense mutation of Arg339-to-Ter (R339X) localizes EPRS1 proteins as polymeric aggregates into Rab7-positive vesicle structures in mouse oligodendroglial FBD-102b cells. Wild-type proteins, in contrast, are distributed throughout the cell bodies. Expression of the R339X mutant proteins, but not the wild-type proteins, in cells induces strong signals regulating Rab7. Whereas cells expressing the wild-type proteins exhibited phenotypes with myelin web-like structures bearing processes following the induction of differentiation, cells expressing the R339X mutant proteins did not. These results indicate that HLD15-associated EPRS1 mutant proteins are localized in Rab7-positive vesicle structures where they modulate Rab7 regulatory signaling, inhibiting cell morphological differentiation. These findings may reveal some of the molecular and cellular pathological mechanisms underlying HLD15.

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“…These variants were correlated with reduced white matter surface area and reduced sulcal width 3 . Other studies identified several SNPs associated with brain-PAD, with the most significant ones located in MAPT 6 and TMEM106B genes 7 . These two genes have been shown to be closely associated with frontotemporal dementia 8 , and MAPT has also been considered as a model of interaction in Parkinson's disease between functional disease outcomes and genetic 9 .…”

Section: Introductionmentioning

confidence: 99%

Brain Age Estimation at Tract Group Level and its Association with Daily Life Measures, Cardiac Risk Factors and Genetic Variants

Salih

Galazzo

Raisi‐Estabragh

et al. 2021

Preprint

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Brain age can be estimated using different MRI modalities including diffusion MRI. Recent studies demonstrated that white matter (WM) tracts that share the same function might experience similar alterations. Therefore, in this work, we sought to investigate such issue focusing on five WM bundles holding that feature that is Association, Brainstem, Commissural, Limbic and Projection fibers, respectively. For each tract group, we estimated brain age for 15335 healthy participants from United Kingdom Biobank relying on diffusion MRI image derived endophenotypes, Bayesian ridge regression modeling and 10 fold-cross validation. Furthermore, we estimated brain age for an ensemble model that gathers all the considered white matter bundles. Association analysis was subsequently performed between the estimated brain age delta as resulting from the six models, that is for each tract group as well as for the ensemble model, and 38 daily life style measures, 14 cardiac risk factors and cardiovascular magnetic resonance imaging features and genetic variants. Our study revealed that the limbic tracts experience less brain aging compared to other tract groups, Brainstem tracts ages relatively faster while the other tract groups present similar brain aging patterns. The model achieved 5.86 mean absolute error (MAE) for brainstem, 5.08 for limbic tracts and around 5.2 for the other three tract groups while, the ensemble model 4.55. Moreover, the results suggest that limbic tracts are more affected by daily lifestyle factors than the other tract groups. Lastly, two SNPs were significantly (p-value < 5E-8) associated with brain age delta in projection fibers. Those SNPs are mapped to HIST1H1A and SLC17A3 genes.

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Physiological and pathological functions of TMEM106B: a gene associated with brain aging and multiple brain disorders

Cited by 62 publications

References 90 publications

Know your enemy and know yourself – the case of SARS-CoV-2 host factors

Know your enemy and know yourself – the case of SARS-CoV-2 host factors

Hypomyelinating Leukodystrophy 15 (HLD15)-Associated Mutation of EPRS1 Leads to Its Polymeric Aggregation in Rab7-Positive Vesicle Structures, Inhibiting Oligodendroglial Cell Morphological Differentiation

Brain Age Estimation at Tract Group Level and its Association with Daily Life Measures, Cardiac Risk Factors and Genetic Variants

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