Forebrain deletion of the dystonia protein torsinA causes dystonic-like movements and loss of striatal cholinergic neurons.

Abstract:

:Striatal dysfunction plays an important role in dystonia, but the striatal cell types that contribute to abnormal movements are poorly defined. We demonstrate that conditional deletion of the DYT1 dystonia protein torsinA in embryonic progenitors of forebrain cholinergic and GABAergic neurons causes dystonic-like twisting movements that emerge during juvenile CNS maturation. The onset of these movements coincides with selective degeneration of dorsal striatal large cholinergic interneurons (LCI), and surviving LCI exhibit morphological, electrophysiological, and connectivity abnormalities. Consistent with the importance of this LCI pathology, murine dystonic-like movements are reduced significantly with an antimuscarinic agent used clinically, and we identify cholinergic abnormalities in postmortem striatal tissue from DYT1 dystonia patients. These findings demonstrate that dorsal LCI have a unique requirement for torsinA function during striatal maturation, and link abnormalities of these cells to dystonic-like movements in an overtly symptomatic animal model.

journal_name

Elife

journal_title

eLife

authors

Pappas SS,Darr K,Holley SM,Cepeda C,Mabrouk OS,Wong JM,LeWitt TM,Paudel R,Houlden H,Kennedy RT,Levine MS,Dauer WT

doi

10.7554/eLife.08352

subject

Has Abstract

pub_date

2015-06-08 00:00:00

pages

e08352

issn

2050-084X

journal_volume

4

pub_type

杂志文章

相关文献

eLife文献大全
  • A year in the life of eLife.

    abstract::Improving the peer review process, overcoming the limitations of print journals and providing open access to the very best work in the life and biomedical sciences are three highlights of our first year. ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.01516

    authors: Schekman R,Watt FM,Weigel D

    更新日期:2013-10-15 00:00:00

  • LEAFY maintains apical stem cell activity during shoot development in the fern Ceratopteris richardii.

    abstract::During land plant evolution, determinate spore-bearing axes (retained in extant bryophytes such as mosses) were progressively transformed into indeterminate branching shoots with specialized reproductive axes that form flowers. The LEAFY transcription factor, which is required for the first zygotic cell division in mo...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.39625

    authors: Plackett AR,Conway SJ,Hewett Hazelton KD,Rabbinowitsch EH,Langdale JA,Di Stilio VS

    更新日期:2018-10-24 00:00:00

  • The haves and the have nots.

    abstract::As the equipment needed to perform state-of-the-art research in many areas of biology becomes ever more expensive, Eve Marder worries that researchers in less wealthy institutions might be left behind. ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.01515

    authors: Marder E

    更新日期:2013-11-19 00:00:00

  • PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells.

    abstract::Mutations in PROP1 are the most common cause of hypopituitarism in humans; therefore, unraveling its mechanism of action is highly relevant from a therapeutic perspective. Our current understanding of the role of PROP1 in the pituitary gland is limited to the repression and activation of the pituitary transcription fa...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.14470

    authors: Pérez Millán MI,Brinkmeier ML,Mortensen AH,Camper SA

    更新日期:2016-06-28 00:00:00

  • Comparison of induced neurons reveals slower structural and functional maturation in humans than in apes.

    abstract::We generated induced excitatory neurons (iNeurons, iNs) from chimpanzee, bonobo, and human stem cells by expressing the transcription factor neurogenin-2 (NGN2). Single-cell RNA sequencing showed that genes involved in dendrite and synapse development are expressed earlier during iNs maturation in the chimpanzee and b...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.59323

    authors: Schörnig M,Ju X,Fast L,Ebert S,Weigert A,Kanton S,Schaffer T,Nadif Kasri N,Treutlein B,Peter BM,Hevers W,Taverna E

    更新日期:2021-01-20 00:00:00

  • Pregnancy success in mice requires appropriate cannabinoid receptor signaling for primary decidua formation.

    abstract::With implantation, mouse stromal cells begin to transform into epithelial-like cells surrounding the implantation chamber forming an avascular zone called the primary decidual zone (PDZ). In the mouse, the PDZ forms a transient, size-dependent permeable barrier to protect the embryo from maternal circulating harmful a...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.61762

    authors: Li Y,Dewar A,Kim YS,Dey SK,Sun X

    更新日期:2020-09-29 00:00:00

  • Nuclear genetic regulation of the human mitochondrial transcriptome.

    abstract::Mitochondria play important roles in cellular processes and disease, yet little is known about how the transcriptional regime of the mitochondrial genome varies across individuals and tissues. By analyzing >11,000 RNA-sequencing libraries across 36 tissue/cell types, we find considerable variation in mitochondrial-enc...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.41927

    authors: Ali AT,Boehme L,Carbajosa G,Seitan VC,Small KS,Hodgkinson A

    更新日期:2019-02-18 00:00:00

  • The major β-catenin/E-cadherin junctional binding site is a primary molecular mechano-transductor of differentiation in vivo.

    abstract::In vivo, the primary molecular mechanotransductive events mechanically initiating cell differentiation remain unknown. Here we find the molecular stretching of the highly conserved Y654-β-catenin-D665-E-cadherin binding site as mechanically induced by tissue strain. It triggers the increase of accessibility of the Y65...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.33381

    authors: Röper JC,Mitrossilis D,Stirnemann G,Waharte F,Brito I,Fernandez-Sanchez ME,Baaden M,Salamero J,Farge E

    更新日期:2018-07-19 00:00:00

  • What single neurons can tell us.

    abstract::IQ scores are correlated with the morphology and activity of certain neurons in the human temporal cortex. ...

    journal_title:eLife

    pub_type: 评论,杂志文章

    doi:10.7554/eLife.44560

    authors: Miller EN,Sherwood CC

    更新日期:2019-02-05 00:00:00

  • Subcellular sequencing of single neurons reveals the dendritic transcriptome of GABAergic interneurons.

    abstract::Although mRNAs are localized in the processes of excitatory neurons, it is still unclear whether interneurons also localize a large population of mRNAs. In addition, the variability in the localized mRNA population within and between cell types is unknown. Here we describe the unbiased transcriptomic characterization ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.63092

    authors: Perez JD,Dieck ST,Alvarez-Castelao B,Tushev G,Chan IC,Schuman EM

    更新日期:2021-01-06 00:00:00

  • Regulation of RUVBL1-RUVBL2 AAA-ATPases by the nonsense-mediated mRNA decay factor DHX34, as evidenced by Cryo-EM.

    abstract::Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that degrades aberrant mRNAs and also regulates the expression of a wide range of physiological transcripts. RUVBL1 and RUVBL2 AAA-ATPases form an hetero-hexameric ring that is part of several macromolecular complexes such as INO80, SWR1, and R2TP. Interesti...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.63042

    authors: López-Perrote A,Hug N,González-Corpas A,Rodríguez CF,Serna M,García-Martín C,Boskovic J,Fernandez-Leiro R,Caceres JF,Llorca O

    更新日期:2020-11-18 00:00:00

  • Assembling the Tat protein translocase.

    abstract::The twin-arginine protein translocation system (Tat) transports folded proteins across the bacterial cytoplasmic membrane and the thylakoid membranes of plant chloroplasts. The Tat transporter is assembled from multiple copies of the membrane proteins TatA, TatB, and TatC. We combine sequence co-evolution analysis, mo...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.20718

    authors: Alcock F,Stansfeld PJ,Basit H,Habersetzer J,Baker MA,Palmer T,Wallace MI,Berks BC

    更新日期:2016-12-03 00:00:00

  • Phosphorylation of β-arrestin2 at Thr383 by MEK underlies β-arrestin-dependent activation of Erk1/2 by GPCRs.

    abstract::In addition to their role in desensitization and internalization of G protein-coupled receptors (GPCRs), β-arrestins are essential scaffolds linking GPCRs to Erk1/2 signaling. However, their role in GPCR-operated Erk1/2 activation differs between GPCRs and the underlying mechanism remains poorly characterized. Here, w...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.23777

    authors: Cassier E,Gallay N,Bourquard T,Claeysen S,Bockaert J,Crépieux P,Poupon A,Reiter E,Marin P,Vandermoere F

    更新日期:2017-02-07 00:00:00

  • Neural coding in barrel cortex during whisker-guided locomotion.

    abstract::Animals seek out relevant information by moving through a dynamic world, but sensory systems are usually studied under highly constrained and passive conditions that may not probe important dimensions of the neural code. Here, we explored neural coding in the barrel cortex of head-fixed mice that tracked walls with th...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.12559

    authors: Sofroniew NJ,Vlasov YA,Hires SA,Freeman J,Svoboda K

    更新日期:2015-12-23 00:00:00

  • Learning multiple variable-speed sequences in striatum via cortical tutoring.

    abstract::Sparse, sequential patterns of neural activity have been observed in numerous brain areas during timekeeping and motor sequence tasks. Inspired by such observations, we construct a model of the striatum, an all-inhibitory circuit where sequential activity patterns are prominent, addressing the following key challenges...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.26084

    authors: Murray JM,Escola GS

    更新日期:2017-05-08 00:00:00

  • Sex-based differences in clearance of chronic Plasmodium falciparum infection.

    abstract::Multiple studies have reported a male bias in incidence and/or prevalence of malaria infection in males compared to females. To test the hypothesis that sex-based differences in host-parasite interactions affect the epidemiology of malaria, we intensively followed Plasmodium falciparum infections in a cohort in a mala...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.59872

    authors: Briggs J,Teyssier N,Nankabirwa JI,Rek J,Jagannathan P,Arinaitwe E,Bousema T,Drakeley C,Murray M,Crawford E,Hathaway N,Staedke SG,Smith D,Rosenthal PJ,Kamya M,Dorsey G,Rodriguez-Barraquer I,Greenhouse B

    更新日期:2020-10-27 00:00:00

  • How lamina-associated polypeptide 1 (LAP1) activates Torsin.

    abstract::Lamina-associated polypeptide 1 (LAP1) resides at the nuclear envelope and interacts with Torsins, poorly understood endoplasmic reticulum (ER)-localized AAA+ ATPases, through a conserved, perinuclear domain. We determined the crystal structure of the perinuclear domain of human LAP1. LAP1 possesses an atypical AAA+ f...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.03239

    authors: Sosa BA,Demircioglu FE,Chen JZ,Ingram J,Ploegh HL,Schwartz TU

    更新日期:2014-08-22 00:00:00

  • A high-resolution morphological and ultrastructural map of anterior sensory cilia and glia in Caenorhabditis elegans.

    abstract::Many primary sensory cilia exhibit unique architectures that are critical for transduction of specific sensory stimuli. Although basic ciliogenic mechanisms are well described, how complex ciliary structures are generated remains unclear. Seminal work performed several decades ago provided an initial but incomplete de...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.01948

    authors: Doroquez DB,Berciu C,Anderson JR,Sengupta P,Nicastro D

    更新日期:2014-03-25 00:00:00

  • sRNA-mediated activation of gene expression by inhibition of 5'-3' exonucleolytic mRNA degradation.

    abstract::Post-transcriptional control by small regulatory RNA (sRNA) is critical for rapid adaptive processes. sRNAs can directly modulate mRNA degradation in Proteobacteria without interfering with translation. However, Firmicutes have a fundamentally different set of ribonucleases for mRNA degradation and whether sRNAs can r...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.23602

    authors: Durand S,Braun F,Helfer AC,Romby P,Condon C

    更新日期:2017-04-24 00:00:00

  • TRAIP drives replisome disassembly and mitotic DNA repair synthesis at sites of incomplete DNA replication.

    abstract::The faithful segregation of eukaryotic chromosomes in mitosis requires that the genome be duplicated completely prior to anaphase. However, cells with large genomes sometimes fail to complete replication during interphase and instead enter mitosis with regions of incompletely replicated DNA. These regions are processe...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.48686

    authors: Sonneville R,Bhowmick R,Hoffmann S,Mailand N,Hickson ID,Labib K

    更新日期:2019-09-23 00:00:00

  • Structural basis for the recognition of spliceosomal SmN/B/B' proteins by the RBM5 OCRE domain in splicing regulation.

    abstract::The multi-domain splicing factor RBM5 regulates the balance between antagonistic isoforms of the apoptosis-control genes FAS/CD95, Caspase-2 and AID. An OCRE (OCtamer REpeat of aromatic residues) domain found in RBM5 is important for alternative splicing regulation and mediates interactions with components of the U4/U...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.14707

    authors: Mourão A,Bonnal S,Soni K,Warner L,Bordonné R,Valcárcel J,Sattler M

    更新日期:2016-11-29 00:00:00

  • Odd-paired is a pioneer-like factor that coordinates with Zelda to control gene expression in embryos.

    abstract::Pioneer factors such as Zelda (Zld) help initiate zygotic transcription in Drosophila early embryos, but whether other factors support this dynamic process is unclear. Odd-paired (Opa), a zinc-finger transcription factor expressed at cellularization, controls the transition of genes from pair-rule to segmental pattern...

    journal_title:eLife

    pub_type: 评论,杂志文章

    doi:10.7554/eLife.59610

    authors: Koromila T,Gao F,Iwasaki Y,He P,Pachter L,Gergen JP,Stathopoulos A

    更新日期:2020-07-23 00:00:00

  • mPFC spindle cycles organize sparse thalamic activation and recently active CA1 cells during non-REM sleep.

    abstract::Sleep oscillations in the neocortex and hippocampus are critical for the integration of new memories into stable generalized representations in neocortex. However, the role of the thalamus in this process is poorly understood. To determine the thalamic contribution to non-REM oscillations (sharp-wave ripples, SWRs; sl...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.48881

    authors: Varela C,Wilson MA

    更新日期:2020-06-11 00:00:00

  • Overtone focusing in biphonic tuvan throat singing.

    abstract::Khoomei is a unique singing style originating from the republic of Tuva in central Asia. Singers produce two pitches simultaneously: a booming low-frequency rumble alongside a hovering high-pitched whistle-like tone. The biomechanics of this biphonation are not well-understood. Here, we use sound analysis, dynamic mag...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.50476

    authors: Bergevin C,Narayan C,Williams J,Mhatre N,Steeves JK,Bernstein JG,Story B

    更新日期:2020-02-17 00:00:00

  • Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K(+) channel.

    abstract::Pore-blocking toxins inhibit voltage-dependent K(+) channels (Kv channels) by plugging the ion-conduction pathway. We have solved the crystal structure of paddle chimera, a Kv channel in complex with charybdotoxin (CTX), a pore-blocking toxin. The toxin binds to the extracellular pore entryway without producing discer...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.00594

    authors: Banerjee A,Lee A,Campbell E,Mackinnon R

    更新日期:2013-05-21 00:00:00

  • Multifactorial processes underlie parallel opsin loss in neotropical bats.

    abstract::The loss of previously adaptive traits is typically linked to relaxation in selection, yet the molecular steps leading to such repeated losses are rarely known. Molecular studies of loss have tended to focus on gene sequences alone, but overlooking other aspects of protein expression might underestimate phenotypic div...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.37412

    authors: Sadier A,Davies KT,Yohe LR,Yun K,Donat P,Hedrick BP,Dumont ER,Dávalos LM,Rossiter SJ,Sears KE

    更新日期:2018-12-18 00:00:00

  • Global DNA methylation remodeling during direct reprogramming of fibroblasts to neurons.

    abstract::Direct reprogramming of fibroblasts to neurons induces widespread cellular and transcriptional reconfiguration. Here, we characterized global epigenomic changes during the direct reprogramming of mouse fibroblasts to neurons using whole-genome base-resolution DNA methylation (mC) sequencing. We found that the pioneer ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.40197

    authors: Luo C,Lee QY,Wapinski O,Castanon R,Nery JR,Mall M,Kareta MS,Cullen SM,Goodell MA,Chang HY,Wernig M,Ecker JR

    更新日期:2019-01-15 00:00:00

  • Adaptation in protein fitness landscapes is facilitated by indirect paths.

    abstract::The structure of fitness landscapes is critical for understanding adaptive protein evolution. Previous empirical studies on fitness landscapes were confined to either the neighborhood around the wild type sequence, involving mostly single and double mutants, or a combinatorially complete subgraph involving only two am...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.16965

    authors: Wu NC,Dai L,Olson CA,Lloyd-Smith JO,Sun R

    更新日期:2016-07-08 00:00:00

  • Homeostatic control of cell wall hydrolysis by the WalRK two-component signaling pathway in Bacillus subtilis.

    abstract::Bacterial cells are encased in a peptidoglycan (PG) exoskeleton that protects them from osmotic lysis and specifies their distinct shapes. Cell wall hydrolases are required to enlarge this covalently closed macromolecule during growth, but how these autolytic enzymes are regulated remains poorly understood. Bacillus s...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.52088

    authors: Dobihal GS,Brunet YR,Flores-Kim J,Rudner DZ

    更新日期:2019-12-06 00:00:00

  • Cell culture-based profiling across mammals reveals DNA repair and metabolism as determinants of species longevity.

    abstract::Mammalian lifespan differs by >100 fold, but the mechanisms associated with such longevity differences are not understood. Here, we conducted a study on primary skin fibroblasts isolated from 16 species of mammals and maintained under identical cell culture conditions. We developed a pipeline for obtaining species-spe...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.19130

    authors: Ma S,Upneja A,Galecki A,Tsai YM,Burant CF,Raskind S,Zhang Q,Zhang ZD,Seluanov A,Gorbunova V,Clish CB,Miller RA,Gladyshev VN

    更新日期:2016-11-22 00:00:00