Molecular basis for dyneinopathies reveals insight into dynein regulation and dysfunction.

Abstract:

:Cytoplasmic dynein plays critical roles within the developing and mature nervous systems, including effecting nuclear migration, and retrograde transport of various cargos. Unsurprisingly, mutations in dynein are causative of various developmental neuropathies and motor neuron diseases. These 'dyneinopathies' define a broad spectrum of diseases with no known correlation between mutation identity and disease state. To circumvent complications associated with dynein studies in human cells, we employed budding yeast as a screening platform to characterize the motility properties of seventeen disease-correlated dynein mutants. Using this system, we determined the molecular basis for several classes of etiologically related diseases. Moreover, by engineering compensatory mutations, we alleviated the mutant phenotypes in two of these cases, one of which we confirmed with recombinant human dynein. In addition to revealing molecular insight into dynein regulation, our data provide additional evidence that the type of disease may in fact be dictated by the degree of dynein dysfunction.

journal_name

Elife

journal_title

eLife

authors

Marzo MG,Griswold JM,Ruff KM,Buchmeier RE,Fees CP,Markus SM

doi

10.7554/eLife.47246

subject

Has Abstract

pub_date

2019-07-31 00:00:00

issn

2050-084X

pii

47246

journal_volume

8

pub_type

杂志文章

相关文献

eLife文献大全
  • Spatially coordinated dynamic gene transcription in living pituitary tissue.

    abstract::Transcription at individual genes in single cells is often pulsatile and stochastic. A key question emerges regarding how this behaviour contributes to tissue phenotype, but it has been a challenge to quantitatively analyse this in living cells over time, as opposed to studying snap-shots of gene expression state. We ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.08494

    authors: Featherstone K,Hey K,Momiji H,McNamara AV,Patist AL,Woodburn J,Spiller DG,Christian HC,McNeilly AS,Mullins JJ,Finkenstädt BF,Rand DA,White MR,Davis JR

    更新日期:2016-02-01 00:00:00

  • Mutual inhibition among postmitotic neurons regulates robustness of brain wiring in Drosophila.

    abstract::Brain connectivity maps display a delicate balance between individual variation and stereotypy, suggesting the existence of dedicated mechanisms that simultaneously permit and limit individual variation. We show that during the development of the Drosophila central nervous system, mutual inhibition among groups of nei...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.00337

    authors: Langen M,Koch M,Yan J,De Geest N,Erfurth ML,Pfeiffer BD,Schmucker D,Moreau Y,Hassan BA

    更新日期:2013-03-05 00:00:00

  • Motor cortex signals for each arm are mixed across hemispheres and neurons yet partitioned within the population response.

    abstract::Motor cortex (M1) has lateralized outputs, yet neurons can be active during movements of either arm. What is the nature and role of activity across the two hemispheres? We recorded muscles and neurons bilaterally while monkeys cycled with each arm. Most neurons were active during movement of either arm. Responses were...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.46159

    authors: Ames KC,Churchland MM

    更新日期:2019-10-09 00:00:00

  • Coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade.

    abstract::Coronaries are essential for myocardial growth and heart function. Notch is crucial for mouse embryonic angiogenesis, but its role in coronary development remains uncertain. We show Jag1, Dll4 and activated Notch1 receptor expression in sinus venosus (SV) endocardium. Endocardial Jag1 removal blocks SV capillary sprou...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.49977

    authors: Travisano SI,Oliveira VL,Prados B,Grego-Bessa J,Piñeiro-Sabarís R,Bou V,Gómez MJ,Sánchez-Cabo F,MacGrogan D,de la Pompa JL

    更新日期:2019-12-04 00:00:00

  • Direct live imaging of cell-cell protein transfer by transient outer membrane fusion in Myxococcus xanthus.

    abstract::In bacteria, multicellular behaviors are regulated by cell-cell signaling through the exchange of both diffusible and contact-dependent signals. In a multicellular context, Myxococcus cells can share outer membrane (OM) materials by an unknown mechanism involving the traAB genes and gliding motility. Using live imagin...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.00868

    authors: Ducret A,Fleuchot B,Bergam P,Mignot T

    更新日期:2013-07-23 00:00:00

  • Three rules govern thalamocortical connectivity of fast-spike inhibitory interneurons in the visual cortex.

    abstract::Some cortical neurons receive highly selective thalamocortical (TC) input, but others do not. Here, we examine connectivity of single thalamic neurons (lateral geniculate nucleus, LGN) onto putative fast-spike inhibitory interneurons in layer 4 of rabbit visual cortex. We show that three 'rules' regulate this connecti...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.60102

    authors: Bereshpolova Y,Hei X,Alonso JM,Swadlow HA

    更新日期:2020-12-08 00:00:00

  • Centering and symmetry breaking in confined contracting actomyosin networks.

    abstract::Centering and decentering of cellular components is essential for internal organization of cells and their ability to perform basic cellular functions such as division and motility. How cells achieve proper localization of their organelles is still not well-understood, especially in large cells such as oocytes. Here, ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.55368

    authors: Ierushalmi N,Malik-Garbi M,Manhart A,Abu Shah E,Goode BL,Mogilner A,Keren K

    更新日期:2020-04-21 00:00:00

  • Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs.

    abstract::Existing in vitro models of human skeletal muscle cannot recapitulate the organization and function of native muscle, limiting their use in physiological and pharmacological studies. Here, we demonstrate engineering of electrically and chemically responsive, contractile human muscle tissues ('myobundles') using primar...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.04885

    authors: Madden L,Juhas M,Kraus WE,Truskey GA,Bursac N

    更新日期:2015-01-09 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

  • Dissecting the phenotypic and functional heterogeneity of mouse inflammatory osteoclasts by the expression of Cx3cr1.

    abstract::Bone destruction relies on interactions between bone and immune cells. Bone-resorbing osteoclasts (OCLs) were recently identified as innate immune cells activating T cells toward tolerance or inflammation. Thus, pathological bone destruction not only relies on increased osteoclast differentiation, but also on the pres...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.54493

    authors: Madel MB,Ibáñez L,Ciucci T,Halper J,Rouleau M,Boutin A,Hue C,Duroux-Richard I,Apparailly F,Garchon HJ,Wakkach A,Blin-Wakkach C

    更新日期:2020-05-13 00:00:00

  • Inference of nonlinear receptive field subunits with spike-triggered clustering.

    abstract::Responses of sensory neurons are often modeled using a weighted combination of rectified linear subunits. Since these subunits often cannot be measured directly, a flexible method is needed to infer their properties from the responses of downstream neurons. We present a method for maximum likelihood estimation of subu...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.45743

    authors: Shah NP,Brackbill N,Rhoades C,Kling A,Goetz G,Litke AM,Sher A,Simoncelli EP,Chichilnisky EJ

    更新日期:2020-03-09 00:00:00

  • bicoid mRNA localises to the Drosophila oocyte anterior by random Dynein-mediated transport and anchoring.

    abstract::bicoid mRNA localises to the Drosophila oocyte anterior from stage 9 of oogenesis onwards to provide a local source for Bicoid protein for embryonic patterning. Live imaging at stage 9 reveals that bicoid mRNA particles undergo rapid Dynein-dependent movements near the oocyte anterior, but with no directional bias. Fu...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.17537

    authors: Trovisco V,Belaya K,Nashchekin D,Irion U,Sirinakis G,Butler R,Lee JJ,Gavis ER,St Johnston D

    更新日期:2016-10-28 00:00:00

  • Organic electrochemical transistor arrays for real-time mapping of evoked neurotransmitter release in vivo.

    abstract::Though neurotransmitters are essential elements in neuronal signal transduction, techniques for in vivo analysis are still limited. Here, we describe an organic electrochemical transistor array (OECT-array) technique for monitoring catecholamine neurotransmitters (CA-NTs) in rat brains. The OECT-array is an active sen...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.50345

    authors: Xie K,Wang N,Lin X,Wang Z,Zhao X,Fang P,Yue H,Kim J,Luo J,Cui S,Yan F,Shi P

    更新日期:2020-02-11 00:00:00

  • Integration of genomics and transcriptomics predicts diabetic retinopathy susceptibility genes.

    abstract::We determined differential gene expression in response to high glucose in lymphoblastoid cell lines derived from matched individuals with type 1 diabetes with and without retinopathy. Those genes exhibiting the largest difference in glucose response were assessed for association with diabetic retinopathy in a genome-w...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.59980

    authors: Skol AD,Jung SC,Sokovic AM,Chen S,Fazal S,Sosina O,Borkar PP,Lin A,Sverdlov M,Cao D,Swaroop A,Bebu I,DCCT\/EDIC Study group.,Stranger BE,Grassi MA

    更新日期:2020-11-09 00:00:00

  • Embryonic transcription factor expression in mice predicts medial amygdala neuronal identity and sex-specific responses to innate behavioral cues.

    abstract::The medial subnucleus of the amygdala (MeA) plays a central role in processing sensory cues required for innate behaviors. However, whether there is a link between developmental programs and the emergence of inborn behaviors remains unknown. Our previous studies revealed that the telencephalic preoptic area (POA) embr...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.21012

    authors: Lischinsky JE,Sokolowski K,Li P,Esumi S,Kamal Y,Goodrich M,Oboti L,Hammond TR,Krishnamoorthy M,Feldman D,Huntsman M,Liu J,Corbin JG

    更新日期:2017-03-13 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

  • Distinct mitochondrial defects trigger the integrated stress response depending on the metabolic state of the cell.

    abstract::Mitochondrial dysfunction is associated with activation of the integrated stress response (ISR) but the underlying triggers remain unclear. We systematically combined acute mitochondrial inhibitors with genetic tools for compartment-specific NADH oxidation to trace mechanisms linking different forms of mitochondrial d...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.49178

    authors: Mick E,Titov DV,Skinner OS,Sharma R,Jourdain AA,Mootha VK

    更新日期:2020-05-28 00:00:00

  • Fish larval recruitment to reefs is a thyroid hormone-mediated metamorphosis sensitive to the pesticide chlorpyrifos.

    abstract::Larval recruitment, the transition of pelagic larvae into reef-associated juveniles, is a critical step for the resilience of marine fish populations but its molecular control is unknown. Here, we investigate whether thyroid-hormones (TH) and their receptors (TR) coordinate the larval recruitment of the coral-reef-fis...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.27595

    authors: Holzer G,Besson M,Lambert A,François L,Barth P,Gillet B,Hughes S,Piganeau G,Leulier F,Viriot L,Lecchini D,Laudet V

    更新日期:2017-10-30 00:00:00

  • 3.3-Å resolution cryo-EM structure of human ribonucleotide reductase with substrate and allosteric regulators bound.

    abstract::Ribonucleotide reductases (RNRs) convert ribonucleotides into deoxyribonucleotides, a reaction essential for DNA replication and repair. Human RNR requires two subunits for activity, the α subunit contains the active site, and the β subunit houses the radical cofactor. Here, we present a 3.3-Å resolution structure by ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.31502

    authors: Brignole EJ,Tsai KL,Chittuluru J,Li H,Aye Y,Penczek PA,Stubbe J,Drennan CL,Asturias F

    更新日期:2018-02-20 00:00:00

  • Ubiquitin-dependent regulation of a conserved DMRT protein controls sexually dimorphic synaptic connectivity and behavior.

    abstract::Sex-specific synaptic connectivity is beginning to emerge as a remarkable, but little explored feature of animal brains. We describe here a novel mechanism that promotes sexually dimorphic neuronal function and synaptic connectivity in the nervous system of the nematode Caenorhabditis elegans. We demonstrate that a ph...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.59614

    authors: Bayer EA,Stecky RC,Neal L,Katsamba PS,Ahlsen G,Balaji V,Hoppe T,Shapiro L,Oren-Suissa M,Hobert O

    更新日期:2020-10-06 00:00:00

  • The age of Homo naledi and associated sediments in the Rising Star Cave, South Africa.

    abstract::New ages for flowstone, sediments and fossil bones from the Dinaledi Chamber are presented. We combined optically stimulated luminescence dating of sediments with U-Th and palaeomagnetic analyses of flowstones to establish that all sediments containing Homo naledi fossils can be allocated to a single stratigraphic ent...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.24231

    authors: Dirks PH,Roberts EM,Hilbert-Wolf H,Kramers JD,Hawks J,Dosseto A,Duval M,Elliott M,Evans M,Grün R,Hellstrom J,Herries AI,Joannes-Boyau R,Makhubela TV,Placzek CJ,Robbins J,Spandler C,Wiersma J,Woodhead J,Berger LR

    更新日期:2017-05-09 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

  • Semiochemical responsive olfactory sensory neurons are sexually dimorphic and plastic.

    abstract::Understanding how genes and experience work in concert to generate phenotypic variability will provide a better understanding of individuality. Here, we considered this in the main olfactory epithelium, a chemosensory structure with over a thousand distinct cell types in mice. We identified a subpopulation of olfactor...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.54501

    authors: Vihani A,Hu XS,Gundala S,Koyama S,Block E,Matsunami H

    更新日期:2020-11-24 00:00:00

  • Conditional deletion of glucocorticoid receptors in rat brain results in sex-specific deficits in fear and coping behaviors.

    abstract::Glucocorticoid receptors (GR) have diverse functions relevant to maintenance of homeostasis and adaptation to environmental challenges. Understanding the importance of tissue-specific GR function in physiology and behavior has been hampered by near-ubiquitous localization in brain and body. Here we use CRISPR/Cas9 gen...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.44672

    authors: Scheimann JR,Moloney RD,Mahbod P,Morano RL,Fitzgerald M,Hoskins O,Packard BA,Cotella EM,Hu YC,Herman JP

    更新日期:2019-07-22 00:00:00

  • Response to short-term deprivation of the human adult visual cortex measured with 7T BOLD.

    abstract::Sensory deprivation during the post-natal 'critical period' leads to structural reorganization of the developing visual cortex. In adulthood, the visual cortex retains some flexibility and adapts to sensory deprivation. Here we show that short-term (2 hr) monocular deprivation in adult humans boosts the BOLD response ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.40014

    authors: Binda P,Kurzawski JW,Lunghi C,Biagi L,Tosetti M,Morrone MC

    更新日期:2018-11-26 00:00:00

  • Interfering with transmission.

    abstract::The IFNλ family of interferons controls the spread of viruses in the upper respiratory tract and transmission between mice. ...

    journal_title:eLife

    pub_type: 评论,杂志文章

    doi:10.7554/eLife.37552

    authors: Wack A

    更新日期:2018-05-24 00:00:00

  • Drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defense.

    abstract::Macrophage-mediated phagocytosis and cytokine production represent the front lines of resistance to bacterial invaders. A key feature of this pro-inflammatory response in mammals is the complex remodeling of cellular metabolism towards aerobic glycolysis. Although the function of bactericidal macrophages is highly con...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.50414

    authors: Krejčová G,Danielová A,Nedbalová P,Kazek M,Strych L,Chawla G,Tennessen JM,Lieskovská J,Jindra M,Doležal T,Bajgar A

    更新日期:2019-10-14 00:00:00

  • The spinal cord is never at rest.

    abstract::Even when we are at rest, our spinal cords show spontaneous, yet well organised, fluctuations of activity that might reflect sensory and motor networks. ...

    journal_title:eLife

    pub_type: 评论,杂志文章

    doi:10.7554/eLife.03811

    authors: Eippert F,Tracey I

    更新日期:2014-08-05 00:00:00

  • Support for a clade of Placozoa and Cnidaria in genes with minimal compositional bias.

    abstract::The phylogenetic placement of the morphologically simple placozoans is crucial to understanding the evolution of complex animal traits. Here, we examine the influence of adding new genomes from placozoans to a large dataset designed to study the deepest splits in the animal phylogeny. Using site-heterogeneous substitu...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.36278

    authors: Laumer CE,Gruber-Vodicka H,Hadfield MG,Pearse VB,Riesgo A,Marioni JC,Giribet G

    更新日期:2018-10-30 00:00:00

  • The Ndc80 complex bridges two Dam1 complex rings.

    abstract::Strong kinetochore-microtubule attachments are essential for faithful segregation of sister chromatids during mitosis. The Dam1 and Ndc80 complexes are the main microtubule binding components of the Saccharomyces cerevisiae kinetochore. Cooperation between these two complexes enhances kinetochore-microtubule coupling ...

    journal_title:eLife

    pub_type: 杂志文章

    doi:10.7554/eLife.21069

    authors: Kim JO,Zelter A,Umbreit NT,Bollozos A,Riffle M,Johnson R,MacCoss MJ,Asbury CL,Davis TN

    更新日期:2017-02-13 00:00:00