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Dynactin

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https://www.readbyqxmd.com/read/27857681/early-cytoskeletal-protein-modifications-precede-overt-structural-degeneration-in-the-dba-2j-mouse-model-of-glaucoma
#1
Gina N Wilson, Matthew A Smith, Denise M Inman, Christine M Dengler-Crish, Samuel D Crish
Axonal transport deficits precede structural loss in glaucoma and other neurodegenerations. Impairments in structural support, including modified cytoskeletal proteins, and microtubule-destabilizing elements, could be initiating factors in glaucoma pathogenesis. We investigated the time course of changes in protein levels and post-translational modifications in the DBA/2J mouse model of glaucoma. Using anterograde tract tracing of the retinal projection, we assessed major cytoskeletal and transported elements as a function of transport integrity in different stages of pathological progression...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27852784/activity-induces-fmr1-sensitive-synaptic-capture-of-anterograde-circulating-neuropeptide-vesicles
#2
Samantha L Cavolo, Dinara Bulgari, David L Deitcher, Edwin S Levitan
: Synaptic neuropeptide and neurotrophin stores are maintained by constitutive bidirectional capture of dense-core vesicles (DCVs) as they circulate in and out of the nerve terminal. Activity increases DCV capture to rapidly replenish synaptic neuropeptide stores following release. However, it is not known whether this is due to enhanced bidirectional capture. Here experiments at the Drosophila neuromuscular junction, where DCVs contain neuropeptides and a bone morphogenic protein, show that activity-dependent replenishment of synaptic neuropeptides following release is evident after inhibiting the retrograde transport with the dynactin disruptor mycalolide B or photobleaching DCVs entering a synaptic bouton by retrograde transport...
November 16, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27802164/nuclear-alignment-in-myotubes-requires-centrosome-proteins-recruited-by-nesprin-1
#3
Aude Espigat-Georger, Vyacheslav Dyachuk, Cécile Chemin, Laurent Emorine, Andreas Merdes
Myotubes are syncytial cells generated by fusion of myoblasts. Among the numerous nuclei in myotubes of skeletal muscle fibres, the majority are equidistantly positioned at the periphery, except for clusters of multiple nuclei underneath the motor endplate. The correct positioning of nuclei is thought to be important for muscle function and requires nesprin-1 (also known as SYNE1), a protein of the nuclear envelope. Consistent with this, mice lacking functional nesprin-1 show defective nuclear positioning and present aspects of Emery-Dreifuss muscular dystrophy...
November 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27789744/protein-pyrophosphorylation-moving-forward
#4
Adolfo Saiardi
Genetic ablation of inositol pyrophosphate synthesis has established the fundamental importance of this class of molecules to the eukaryote cell. These studies, however, must be complemented by cell biology and biochemical approaches to appreciate the signalling involved in the processes regulated by inositol pyrophosphates. A recent study by Chanduri et al. published in the Biochemical Journal, by integrating multiple experimental approaches, demonstrated that inositol pyrophosphates regulate intracellular vesicular movement...
November 1, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27742209/knockdown-of-dynamitin-in-testes-significantly-decreased-male-fertility-in-drosophila-melanogaster
#5
Chun-Hong Wu, Qiong Zong, An-Li Du, Wei Zhang, Han-Chao Yao, Xiao-Qiang Yu, Yu-Feng Wang
Dynamitin (Dmn) is a major component of dynactin, a multiprotein complex playing important roles in a variety of intracellular motile events. We previously found that Wolbachia bacterial infection resulted in a reduction of Dmn protein. As Wolbachia may modify sperm in male hosts, we speculate that Dmn may have a function in male fertility. Here we used nosGal4 to drive Dmn knock down in testes of Drosophila melanogaster to investigate the functions of Dmn in spermatogenesis. We found that knockdown of Dmn in testes dramatically decreased male fertility, overexpression of Dmn in Wolbachia-infected males significantly rescued male fertility, indicating an important role of Dmn in inducing male fertility defects following Wolbachia infection...
December 1, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27718357/ankyrin-b-is-a-pi3p-effector-that-promotes-polarized-%C3%AE-5%C3%AE-1-integrin-recycling-via-recruiting-rabgap1l-to-early-endosomes
#6
Fangfei Qu, Damaris N Lorenzo, Samantha J King, Rebecca Brooks, James E Bear, Vann Bennett
Endosomal membrane trafficking requires coordination between phosphoinositide lipids, Rab GTPases, and microtubule-based motors to dynamically determine endosome identity and promote long-range organelle transport. Here we report that ankyrin-B (AnkB), through integrating all three systems, functions as a critical node in the protein circuitry underlying polarized recycling of α5β1-integrin in mouse embryonic fibroblasts, which enables persistent fibroblast migration along fibronectin gradients. AnkB associates with phosphatidylinositol 3-phosphate (PI3P)-positive organelles in fibroblasts and binds dynactin to promote their long-range motility...
October 8, 2016: ELife
https://www.readbyqxmd.com/read/27689404/in-vivo-phage-display-screening-for-tumor-vascular-targets-in-glioblastoma-identifies-a-llama-nanobody-against-dynactin-1-p150glued
#7
Sanne A M van Lith, Ilse Roodink, Joost J C Verhoeff, Petri I Mäkinen, Jari P Lappalainen, Seppo Ylä-Herttuala, Jos Raats, Erwin van Wijk, Ronald Roepman, Stef J Letteboer, Kiek Verrijp, William P J Leenders
Diffuse gliomas are primary brain cancers that are characterised by infiltrative growth. Whereas high-grade glioma characteristically presents with perinecrotic neovascularisation, large tumor areas thrive on pre-existent vasculature as well. Clinical studies have revealed that pharmacological inhibition of the angiogenic process does not improve survival of glioblastoma patients. Direct targeting of tumor vessels may however still be an interesting therapeutic approach as it allows pinching off the blood supply to tumor cells...
September 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27672093/mitotic-spindle-positioning-in-the-ems-cell-of-caenorhabditis-elegans-requires-let-99-and-lin-5-numa
#8
Malgorzata J Liro, Lesilee S Rose
Asymmetric divisions produce daughter cells with different fates, and thus are critical for animal development. During asymmetric divisions, the mitotic spindle must be positioned on a polarized axis to ensure the differential segregation of cell fate determinants into the daughter cells. In many cell types a cortically localized complex consisting of Gα, GPR-1/2, and LIN-5 (Gαi/Pins/Mud, Gαi/LGN/NuMA) mediates the recruitment of dynactin/dynein, which exerts pulling forces on astral microtubules to physically position the spindle...
September 26, 2016: Genetics
https://www.readbyqxmd.com/read/27668583/evaluation-of-the-dynactin-1-gene-in-leonbergers-and-labrador-retrievers-with-laryngeal-paralysis
#9
David E Holt, Dorothy C Brown, Paula S Henthorn
OBJECTIVE To sequence exons and splice consensus sites of the dynactin subunit 1 (DCTN1) gene in Leonbergers and Labrador Retrievers with clinical laryngeal paralysis. ANIMALS 5 unrelated Leonbergers with laryngeal paralysis, 2 clinically normal Leonbergers, 7 unrelated Labrador Retrievers with laryngeal paralysis, and 2 clinically normal Labrador Retrievers. PROCEDURES Primers were designed for the entire coding regions of the DCTN1 gene, a noncoding exon at the 5´ end of the gene, and a 900-bp single-nucleotide polymorphism (SNP)-rich region located 17 kb upstream of the DCTN1 gene by use of the CanFam3 assembly of the canine genome sequence...
October 2016: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/27573046/distal-hereditary-motor-neuropathy-type%C3%A2-7b-with-dynactin-1-mutation
#10
Sun Hee Hwang, Eun Ja Kim, Young Bin Hong, Jaesoon Joo, Sung Min Kim, Soo Hyun Nam, Hyun Dae Hong, Seung Hyun Kim, Kiwook Oh, Jeong-Geun Lim, Jeong Hee Cho, Ki Wha Chung, Byung-Ok Choi
Mutations in the Dynactin 1 (DCTN1) gene have been demonstrated to result in various neurodegenerative diseases, including distal hereditary motor neuropathy type 7B (dHMN7B), Perry syndrome, amyotrophic lateral sclerosis and amyotrophic lateral sclerosis‑frontotemporal dementia. However, since the first dHMN7B patient with a DCTN1 mutation was described in 2003, to the best of our knowledge no further cases have been reported. In the present study, the DCTN1 p.G59S mutation was identified in two unrelated families from a total of 24 Korean families with dHMN, by whole exome sequencing...
October 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27559151/a-network-medicine-approach-to-build-a-comprehensive-atlas-for-the-prognosis-of-human-cancer
#11
Fan Zhang, Chunyan Ren, Kwun Kit Lau, Zihan Zheng, Geming Lu, Zhengzi Yi, Yongzhong Zhao, Fei Su, Shaojun Zhang, Bin Zhang, Eric A Sobie, Weijia Zhang, Martin J Walsh
The Cancer Genome Atlas project has generated multi-dimensional and highly integrated genomic data from a large number of patient samples with detailed clinical records across many cancer types, but it remains unclear how to best integrate the massive amount of genomic data into clinical practice. We report here our methodology to build a multi-dimensional subnetwork atlas for cancer prognosis to better investigate the potential impact of multiple genetic and epigenetic (gene expression, copy number variation, microRNA expression and DNA methylation) changes on the molecular states of networks that in turn affects complex cancer survivorship...
August 24, 2016: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/27559088/rab5-and-its-effector-fhf-contribute-to-neuronal-polarity-through-dynein-dependent-retrieval-of-somatodendritic-proteins-from-the-axon
#12
Xiaoli Guo, Ginny G Farías, Rafael Mattera, Juan S Bonifacino
An open question in cell biology is how the general intracellular transport machinery is adapted to perform specialized functions in polarized cells such as neurons. Here we illustrate this adaptation by elucidating a role for the ubiquitous small GTPase Ras-related protein in brain 5 (Rab5) in neuronal polarity. We show that inactivation or depletion of Rab5 in rat hippocampal neurons abrogates the somatodendritic polarity of the transferrin receptor and several glutamate receptor types, resulting in their appearance in the axon...
September 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27550070/rab24-interacts-with-the-rab7-rab-interacting-lysosomal-protein-complex-to-regulate-endosomal-degradation
#13
Celina Amaya, Rodrigo D Militello, Sebastián D Calligaris, María I Colombo
Endocytosis is a multistep process engaged in extracellular molecules internalization. Several proteins including the Rab GTPases family coordinate the endocytic pathway. The small GTPase Rab7 is present in late endosome (LE) compartments being a marker of endosome maturation. The Rab interacting lysosomal protein (RILP) is a downstream effector of Rab7 that recruits the functional dynein/dynactin motor complex to late compartments. In the present study, we have found Rab24 as a component of the endosome-lysosome degradative pathway...
August 23, 2016: Traffic
https://www.readbyqxmd.com/read/27534551/dynein-separately-partners-with-nde1-and-dynactin-to-orchestrate-t-cell-focused-secretion
#14
Shubhankar Nath, Laura Christian, Sarah Youngsun Tan, Sanghee Ki, Lauren I R Ehrlich, Martin Poenie
Helper and cytotoxic T cells accomplish focused secretion through the movement of vesicles toward the microtubule organizing center (MTOC) and translocation of the MTOC to the target contact site. In this study, using Jurkat cells and OT-I TCR transgenic primary murine CTLs, we show that the dynein-binding proteins nuclear distribution E homolog 1 (NDE1) and dynactin (as represented by p150(Glued)) form mutually exclusive complexes with dynein, exhibit nonoverlapping distributions in target-stimulated cells, and mediate different transport events...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27503910/hsp90-binding-immunophilin-fkbp52-modulates-telomerase-activity-by-promoting-the-cytoplasmic-retrotransport-of-htert
#15
Yu Young Jeong, Joonyoung Her, Sue-Young Oh, In Kwon Chung
Telomerase is a unique ribonucleoprotein enzyme that is required for continued cell proliferation. To generate catalytically active telomerase, human telomerase reverse transcriptase (hTERT) must translocate to the nucleus and assemble with the RNA component of telomerase. The molecular chaperones heat shock protein 90 (Hsp90) and p23 maintain hTERT in a conformation that enables nuclear translocation. However, the regulatory role of chaperones in nuclear transport of hTERT remains unclear. In this work, we demonstrate that immunophilin FK506-binding protein (FKBP)52 linked the hTERT-Hsp90 complex to the dynein-dynactin motor, thereby promoting the transport of hTERT to the nucleus along microtubules...
October 15, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27489054/load-induced-enhancement-of-dynein-force-production-by-lis1-nude-in-vivo-and-in-vitro
#16
Babu J N Reddy, Michelle Mattson, Caitlin L Wynne, Omid Vadpey, Abdo Durra, Dail Chapman, Richard B Vallee, Steven P Gross
Most sub-cellular cargos are transported along microtubules by kinesin and dynein molecular motors, but how transport is regulated is not well understood. It is unknown whether local control is possible, for example, by changes in specific cargo-associated motor behaviour to react to impediments. Here we discover that microtubule-associated lipid droplets (LDs) in COS1 cells respond to an optical trap with a remarkable enhancement in sustained force production. This effect is observed only for microtubule minus-end-moving LDs...
2016: Nature Communications
https://www.readbyqxmd.com/read/27474409/inositol-hexakisphosphate-kinase-1-ip6k1-activity-is-required-for-cytoplasmic-dynein-driven-transport
#17
Manasa Chanduri, Ashim Rai, Aushaq Bashir Malla, Mingxuan Wu, Dorothea Fiedler, Roop Mallik, Rashna Bhandari
Inositol pyrophosphates, such as diphosphoinositol pentakisphosphate (IP7), are conserved eukaryotic signaling molecules that possess pyrophosphate and monophosphate moieties. Generated predominantly by inositol hexakisphosphate kinases (IP6Ks), inositol pyrophosphates can modulate protein function by posttranslational serine pyrophosphorylation. Here, we report inositol pyrophosphates as novel regulators of cytoplasmic dynein-driven vesicle transport. Mammalian cells lacking IP6K1 display defects in dynein-dependent trafficking pathways, including endosomal sorting, vesicle movement, and Golgi maintenance...
October 1, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27462449/the-interchange-of-immunophilins-leads-to-parallel-pathways-and-different-intermediates-in-the-assembly-of-hsp90-glucocorticoid-receptor-complexes
#18
Ima-Obong Ebong, Victoria Beilsten-Edmands, Nisha A Patel, Nina Morgner, Carol V Robinson
Hormone receptors require participation of the chaperones Hsp40/Hsp70 to form client-transfer complexes with Hsp90/Hop. Interaction with the co-chaperone p23 releases Hop and Hsp70, and the immunophilin FKBP52 mediates transfer of the Hsp90-receptor complex to the nucleus. Inhibition of glucocorticoid receptor (GR) transport by FKBP51, but not by FKBP52, has been observed at the cellular level, but the subunit composition of the intermediates involved has not been deduced. Here we use mass spectrometry to show that FKBP51/52 form analogous complexes with GR/Hsp90/Hop/Hsp70/ATP, but differences emerge upon addition of p23 to client-transfer complexes...
2016: Cell Discovery
https://www.readbyqxmd.com/read/27454819/the-mammalian-dynein-dynactin-complex-is-a-strong-opponent-to-kinesin-in-a-tug-of-war-competition
#19
Vladislav Belyy, Max A Schlager, Helen Foster, Armando E Reimer, Andrew P Carter, Ahmet Yildiz
Kinesin and dynein motors transport intracellular cargos bidirectionally by pulling them in opposite directions along microtubules, through a process frequently described as a 'tug of war'. While kinesin produces 6 pN of force, mammalian dynein was found to be a surprisingly weak motor (0.5-1.5 pN) in vitro, suggesting that many dyneins are required to counteract the pull of a single kinesin. Mammalian dynein's association with dynactin and Bicaudal-D2 (BICD2) activates its processive motility, but it was unknown how this affects dynein's force output...
September 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27365401/hook-adaptors-induce-unidirectional-processive-motility-by-enhancing-the-dynein-dynactin-interaction
#20
Mara A Olenick, Mariko Tokito, Malgorzata Boczkowska, Roberto Dominguez, Erika L F Holzbaur
Cytoplasmic dynein drives the majority of minus end-directed vesicular and organelle motility in the cell. However, it remains unclear how dynein is spatially and temporally regulated given the variety of cargo that must be properly localized to maintain cellular function. Recent work has suggested that adaptor proteins provide a mechanism for cargo-specific regulation of motors. Of particular interest, studies in fungal systems have implicated Hook proteins in the regulation of microtubule motors. Here we investigate the role of mammalian Hook proteins, Hook1 and Hook3, as potential motor adaptors...
August 26, 2016: Journal of Biological Chemistry
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