Abstract:
:Mutations in GRN, which encodes progranulin, are a common cause of familial frontotemporal dementia (FTD). FTD is a devastating disease characterised by neuronal loss in the frontal and temporal lobes that leads to changes in personality, behaviour and language. There are no effective treatments for this complex condition. TMEM106B is a well-recognised risk factor for FTD caused by GRN mutation. While the specific relationship between progranulin and TMEM106B is unclear, it is well established that they are both required for correct lysosome function and trafficking. Elegant experiments have suggested that increased risk for FTD is due to elevated levels of TMEM106B (Nicholson et al, 2013; Gallagher et al, 2017). Therefore, recent work has explored the therapeutic potential of reducing TMEM106B levels, with initial results looking encouraging, as crossing a Grn-deficient mouse to a Tmem106b knockout showed a rescue in FTD-related behavioural defects and specific aspects of lysosome dysfunction (Klein et al, 2017). However, three independent studies in this issue report that completely removing Tmem106b from Grn knockout mice leads to clear exacerbation of phenotypes, causing severe motor deficits, neurodegeneration and enhanced lysosome abnormalities and gliosis. Remarkably, the double knockout mice also develop TDP-43 pathology-a hallmark of FTD patients with GRN mutations that have not been consistently observed in either of the single knockouts. These concurrent publications that all reach the same surprising but definitive conclusion are a cautionary tale in the control of TMEM106B levels as a potential therapeutic for FTD. They also re-ignite the debate as to whether loss or gain of TMEM106B function is critical for altering FTD risk.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Clayton EL,Isaacs AMdoi
10.15252/embr.202051668subject
Has Abstractpub_date
2020-10-05 00:00:00pages
e51668issue
10eissn
1469-221Xissn
1469-3178journal_volume
21pub_type
杂志文章相关文献
EMBO REPORTS文献大全abstract::N6-methyladenosine (m6A) is a highly dynamic RNA modification that has recently emerged as a key regulator of gene expression. While many m6A modifications are installed by the METTL3-METTL14 complex, others appear to be introduced independently, implying that additional human m6A methyltransferases remain to be ident...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201744940
更新日期:2017-11-01 00:00:00
abstract::Although Niban is highly expressed in human cancer cells, the cellular functions of Niban remain largely unknown. We demonstrate here that ultraviolet irradiation induces phosphorylation of Niban at S602 by AKT, which increases the association of Niban with nucleophosmin and disassociation of nucleophosmin from the MD...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/embor.2012.53
更新日期:2012-06-01 00:00:00
abstract::The bacterium Bacillus subtilis produces the DNA integrity scanning protein (DisA), a checkpoint protein that delays sporulation in response to DNA damage. DisA scans the chromosome and pauses at sites of DNA lesions. Structural analysis showed that DisA synthesizes the small molecule cyclic diadenosine monophosphate ...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/embor.2011.77
更新日期:2011-06-01 00:00:00
abstract::The energetic metabolism of photosynthetic organisms is profoundly influenced by state transitions and cyclic electron flow around photosystem I. The former involve a reversible redistribution of the light-harvesting antenna between photosystem I and photosystem II and optimize light energy utilization in photosynthes...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1093/embo-reports/kvf047
更新日期:2002-03-01 00:00:00
abstract::The role of long noncoding RNAs (lncRNAs) in viral infection is poorly studied. We have identified hepatitis C virus (HCV)-Stimulated lncRNAs (CSRs) by transcriptome analysis. Interestingly, two of these CSRs (PVT1 and UCA1) play relevant roles in tumorigenesis, providing a novel link between HCV infection and develop...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201541763
更新日期:2016-07-01 00:00:00
abstract::The cytosolic pathogen sensor RIG-I is activated by RNAs with exposed 5'-triphosphate (5'-ppp) and terminal double-stranded structures, such as those that are generated during viral infection. RIG-I has been shown to translocate on dsRNA in an ATP-dependent manner. However, the precise role of the ATPase activity in R...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/embor.2013.102
更新日期:2013-09-01 00:00:00
abstract::X inactivation is the mechanism by which mammals adjust the genetic imbalance that arises from the different numbers of gene-rich X-chromosomes between the sexes. The dosage difference between XX females and XY males is functionally equalized by silencing one of the two X chromosomes in females. This dosage-compensati...
journal_title:EMBO reports
pub_type: 杂志文章,评审
doi:10.1038/sj.embor.7400871
更新日期:2007-01-01 00:00:00
abstract::Reading the academic literature is an essential part of a scientist's job. David Smith argues that reading fiction can be even more important for creativity and productivity than papers and reviews. ...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.202052206
更新日期:2021-01-04 00:00:00
abstract::RNA editing in plant organelles is mediated by site-specific, nuclear-encoded factors. Previous data suggested that the maintenance of these factors depends on the presence of their rapidly evolving cognate sites. The surprising ability of allotetraploid Nicotiana tabacum (tobacco) to edit a foreign site in the chloro...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400619
更新日期:2006-03-01 00:00:00
abstract::DNA repair by homologous recombination is involved in maintaining genome stability. Previous data report that wild-type p53 suppresses homologous recombination and physically interacts with Rad51. Here, we show the in vivo binding of wild-type p53 to a p53 response element in the promoter of Rad51 and the downregulati...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400587
更新日期:2006-02-01 00:00:00
abstract::The aggregation of the two yeast proteins Sup35p and Ure2p is widely accepted as a model for explaining the prion propagation of the phenotypes [PSI+] and [URE3], respectively. Here, we demonstrate that the propagation of [URE3] cannot simply be the consequence of generating large aggregates of Ure2p, because such agg...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1093/embo-reports/kvf011
更新日期:2002-01-01 00:00:00
abstract::The eukaryotic GINS complex has an essential role in the initiation and elongation phases of genome duplication. It is composed of four paralogous subunits--Sld5, Psf1, Psf2 and Psf3--which are ubiquitous and evolutionarily conserved in eukaryotic organisms. Here, we report the biochemical characterization of the huma...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400870
更新日期:2007-01-01 00:00:00
abstract::The structure of the DNA-binding NAC domain of Arabidopsis ANAC (abscisic-acid-responsive NAC) has been determined by X-ray crystallography to 1.9A resolution (Protein Data Bank codes 1UT4 and 1UT7). This is the first structure determined for a member of the NAC family of plant-specific transcriptional regulators. NAC...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400093
更新日期:2004-03-01 00:00:00
abstract::Mutations in the death domain of the death receptor CD95 (APO-1/Fas) cause lymphoproliferation and autoimmune disease in both lpr(cg) mice and in patients with autoimmune lymphoproliferative syndrome (ALPS) type Ia. By testing lymphocytes from ALPS type Ia patients, comparing heterozygous with homozygous lpr(cg) mice ...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400280
更新日期:2004-11-01 00:00:00
abstract::Alternative RNA processing of LMNA pre-mRNA produces three main protein isoforms, that is, lamin A, progerin, and lamin C. De novo mutations that favor the expression of progerin over lamin A lead to Hutchinson-Gilford progeria syndrome (HGPS), providing support for the involvement of LMNA processing in pathological a...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1002/embr.201338126
更新日期:2014-05-01 00:00:00
abstract::Mitochondria play a central role in stem cell homeostasis. Reversible switching between aerobic and anaerobic metabolism is critical for stem cell quiescence, multipotency, and differentiation, as well as for cell reprogramming. However, the effect of mitochondrial dysfunction on neural stem cell (NSC) function is uns...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201540982
更新日期:2015-11-01 00:00:00
abstract::The Polycomb group (PcG) of proteins conveys epigenetic inheritance of repressed transcriptional states. In Drosophila, the Polycomb repressive complex 1 (PRC1) maintains the silent state by inhibiting the transcription machinery and chromatin remodelling at core promoters. Using immunoprecipitation of in vivo formald...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400260
更新日期:2004-10-01 00:00:00
abstract::Nuclear components are functionally linked with the dynamic temporal and spatial compartmentalization, sorting and integration of regulatory information to facilitate its selective use. For example, the subnuclear targeting of transcription factors to punctate sites in the interphase nucleus mechanistically couples ch...
journal_title:EMBO reports
pub_type: 杂志文章,评审
doi:10.1038/sj.embor.7400337
更新日期:2005-02-01 00:00:00
abstract::The race for a vaccine against SARS-CoV-2 has accelerated research on RNA-based therapeutics. Beyond vaccines, RNA also shows great potential for cancer therapies. ...
journal_title:EMBO reports
pub_type: 评论,杂志文章
doi:10.15252/embr.202051013
更新日期:2020-07-03 00:00:00
abstract::In Drosophila melanogaster males, X-chromosome monosomy is compensated by chromosome-wide transcription activation. We found that complete dosage compensation during embryogenesis takes surprisingly long and is incomplete even after 10 h of development. Although the activating dosage compensation complex (DCC) associa...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201948138
更新日期:2019-08-01 00:00:00
abstract::KCC2, encoded in humans by the SLC12A5 gene, is a multifunctional neuron-specific protein initially identified as the chloride (Cl- ) extruder critical for hyperpolarizing GABAA receptor currents. Independently of its canonical function as a K-Cl cotransporter, KCC2 regulates the actin cytoskeleton via molecular inter...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201948880
更新日期:2020-04-03 00:00:00
abstract::Drosophila ovarian germline stem cells (GSCs) are maintained by the extracellular BMP2/4 orthologue Dpp, which is produced from the surrounding somatic niche. The Dpp signal has a short range; it induces a response in GSCs within the niche, but is rapidly extinguished in their progeny only one cell-diameter away. To e...
journal_title:EMBO reports
pub_type: 杂志文章,评审
doi:10.1038/embor.2011.80
更新日期:2011-06-01 00:00:00
abstract::The intracellular modification of proteins by the addition of a single O-linked N-acetylglucosamine (O-GlcNAc) molecule is a ubiquitous post-translational modification in eukaryotic cells. It is catalysed by O-linked N-acetylglucosaminyltransferase, which attaches O-GlcNAc to serine/threonine residues, and it is count...
journal_title:EMBO reports
pub_type: 杂志文章,评审
doi:10.1038/embor.2008.129
更新日期:2008-08-01 00:00:00
abstract::The imprint at the mat1 locus of Schizosaccharomyces pombe acts to initiate the replication-coupled recombination event that underlies mating-type switching. However, the nature of the imprint has been an area of dispute. Two alternative models have been proposed: one stated that the imprint is a nick in the DNA, wher...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400576
更新日期:2006-01-01 00:00:00
abstract::Mammalian artificial chromosomes (MACs) provide a new tool for the improvement of our knowledge of chromosome structure and function. Moreover, they constitute an alternative and potentially powerful tool for gene delivery both in cultured cells and for the production of transgenic animals. In the present work we desc...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1093/embo-reports/kve018
更新日期:2001-02-01 00:00:00
abstract::The gastrointestinal tract undergoes homeostatic self-renewal to replace aged and damaged epithelial cells. This process, sustained by intestinal stem cells (ISCs), can operate accurately for many years but gradually declines with age. Although stem cell aging has been intensively explored, the mechanisms remain poorl...
journal_title:EMBO reports
pub_type: 评论,新闻
doi:10.15252/embr.202051175
更新日期:2020-08-05 00:00:00
abstract::Mitochondrial respiration generates an electrochemical proton gradient across the mitochondrial inner membrane called protonmotive force (PMF) to drive diverse functions and synthesize ATP. Current techniques to manipulate the PMF are limited to its dissipation; yet, there is no precise and reversible method to increa...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201949113
更新日期:2020-04-03 00:00:00
abstract::The major DNA methyltransferase, Dnmt1, associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand. In view of the slow kinetics of Dnmt1 in vitro versus the fast progression of the replication fork, we have tested whether Dnmt1 associates with chromatin beyond...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400295
更新日期:2004-12-01 00:00:00
abstract::The components and pathways that regulate and execute developmental cell death programmes in plants remain largely unknown. We have found that the PROMOTION OF CELL SURVIVAL 1 (PCS1) gene in Arabidopsis, which encodes an aspartic protease, has an important role in determining the fate of cells in embryonic development...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400357
更新日期:2005-03-01 00:00:00
abstract::The biosynthesis of RNA includes its post-transcriptional modifications, and the crucial functions of these modifications have supported their conservation within all three kingdoms. For example, the modifications located within or adjacent to the anticodon of the transfer RNA (tRNA) enhance the accuracy of codon bind...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/embor.2008.104
更新日期:2008-07-01 00:00:00