keyword
MENU ▼
Read by QxMD icon Read
search

Dynactin

keyword
https://www.readbyqxmd.com/read/28320824/molecular-mechanism-of-dynein-recruitment-to-kinetochores-by-the-rod-zw10-zwilch-complex-and-spindly
#1
José B Gama, Cláudia Pereira, Patrícia A Simões, Ricardo Celestino, Rita M Reis, Daniel J Barbosa, Helena R Pires, Cátia Carvalho, João Amorim, Ana X Carvalho, Dhanya K Cheerambathur, Reto Gassmann
The molecular motor dynein concentrates at the kinetochore region of mitotic chromosomes in animals to accelerate spindle microtubule capture and to control spindle checkpoint signaling. In this study, we describe the molecular mechanism used by the Rod-Zw10-Zwilch complex and the adaptor Spindly to recruit dynein to kinetochores in Caenorhabditis elegans embryos and human cells. We show that Rod's N-terminal β-propeller and the associated Zwilch subunit bind Spindly's C-terminal domain, and we identify a specific Zwilch mutant that abrogates Spindly and dynein recruitment in vivo and Spindly binding to a Rod β-propeller-Zwilch complex in vitro...
March 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28248450/regulation-of-dynein-dynactin-driven-vesicular-transport
#2
REVIEW
Jia-Jia Liu
Most of the long-range intracellular movements of vesicles, organelles and other cargoes are driven by microtubule-based molecular motors. Cytoplasmic dynein, a multisubunit protein complex, with the aid of dynactin, drives transport of a wide variety of cargoes towards the minus end of microtubules. In the present article, we review our current understanding of the mechanisms underlying spatiotemporal regulation of dynein-dynactin-driven vesicular transport with a special emphasis on the many steps of directional movement along microtubule tracks...
March 1, 2017: Traffic
https://www.readbyqxmd.com/read/28218281/ubiquitination-and-dynactin-regulate-tmepai-lysosomal-trafficking
#3
Shenheng Luo, Lei Jing, Tian Zhao, Yuyin Li, Zhenxing Liu, Aipo Diao
The transmembrane prostate androgen-induced protein (TMEPAI) has been reported to be elevated in various tumor cells, is localized to the lysosome and promotes lysosome stability. The molecular mechanism of TMEPAI trafficking however to the lysosome is unknown. Here we report that clathrin and CI-M6PR mediate TMEPAI transport from the Golgi directly into the endo-lysosomal pathway. TMEPAI is ubiquitinated at its C-terminal region and ubiquitination modification of TMEPAI is a signal for its lysosomal trafficking...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209731/transport-of-fungal-rab11-secretory-vesicles-involves-myosin-5-dynein-dynactin-p25-and-kinesin-1-and-is-independent-of-kinesin-3
#4
Miguel A Peñalva, Jun Zhang, Xin Xiang, Areti Pantazopoulou
Hyphal tip cells of the fungus Aspergillus nidulans are useful to study long-range intracellular traffic. Post-Golgi secretory vesicles (SVs) containing the RAB11 orthologue RabE engage myosin-5 as well as plus-end- and minus-end-directed microtubule motors, providing an experimental system to investigate the interplay between microtubule and actin motors acting on the same cargo. By exploiting the fact that depolymerization of F-actin 'unleashes' SVs focused at the apex by myosin-5 to microtubule-dependent motors, we establish that the minus-end directed transport of SVs requires the dynein/dynactin supercomplex...
February 16, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28196890/dync1h1-mutations-associated-with-neurological-diseases-compromise-processivity-of-dynein-dynactin-cargo-adaptor-complexes
#5
Ha Thi Hoang, Max A Schlager, Andrew P Carter, Simon L Bullock
Mutations in the human DYNC1H1 gene are associated with neurological diseases. DYNC1H1 encodes the heavy chain of cytoplasmic dynein-1, a 1.4-MDa motor complex that traffics organelles, vesicles, and macromolecules toward microtubule minus ends. The effects of the DYNC1H1 mutations on dynein motility, and consequently their links to neuropathology, are not understood. Here, we address this issue using a recombinant expression system for human dynein coupled to single-molecule resolution in vitro motility assays...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28162951/dynein-binding-of-competitive-regulators-dynactin-and-nude-involves-novel-interplay-between-phosphorylation-site-and-disordered-spliced-linkers
#6
Jing Jie, Frank Löhr, Elisar Barbar
Dynactin and NudE/Nudel are prominent regulators of cytoplasmic dynein motility and cargo-binding activities. Both interact with the intrinsically disordered N-terminal domain of dynein intermediate chain (IC), which also contains phosphorylation sites that apparently regulate these interactions. Nuclear magnetic resonance and isothermal calorimetry studies demonstrate that the Ser84 phosphorylation site identified in cells is in a disordered linker distant from the N-terminal helix that contains both the dynactin- and the Nudel-binding interfaces...
March 7, 2017: Structure
https://www.readbyqxmd.com/read/28131906/a-novel-hdac6-inhibitor-tubastatin-a-controls-hdac6-p97-vcp-mediated-ubiquitination-autophagy-turnover-and-reverses-temozolomide-induced-er-stress-tolerance-in-gbm-cells
#7
Zong-Yang Li, Ce Zhang, Yuan Zhang, Lei Chen, Bao-Dong Chen, Qing-Zhong Li, Xie-Jun Zhang, Wei-Ping Li
Temozolomide (TMZ) is the cornerstone of therapy for glioblastoma multiforme (GBM). However, its efficacy is limited due to the development of multidrug resistance (MDR). In this study, we first identified the occurrence of ER stress-tolerance (ERST) in glioma cells and confirmed that ERST was positively correlated with TMZ resistance. We further showed that the seesaw-effect of HDAC6-p97/VCP (increased HDAC6 and decreased p97/VCP) in glioma cells was crucial to ERST-associated TMZ resistance. Moreover, the combination treatment of Tubastatin A (TUB, a selective inhibitor of HDAC6) and TMZ synergistically overcame ERST, reduced cell viability and induced apoptosis in TMZ-resistant glioma cells...
January 26, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28120201/mapping-protein-protein-interactions-by-double-redor-filtered-magic-angle-spinning-nmr-spectroscopy
#8
Changmiao Guo, Guangjin Hou, Xingyu Lu, Tatyana Polenova
REDOR-based experiments with simultaneous (1)H-(13)C and (1)H-(15)N dipolar dephasing are explored for investigating intermolecular protein-protein interfaces in complexes formed by a U-(13)C,(15)N-labeled protein and its natural abundance binding partner. The application of a double-REDOR filter (dREDOR) results in a complete dephasing of proton magnetization in the U-(13)C,(15)N-enriched molecule while the proton magnetization of the unlabeled binding partner is not dephased. This retained proton magnetization is then transferred across the intermolecular interface by (1)H-(13)C or (1)H-(15)N cross polarization, permitting to establish the residues of the U-(13)C,(15)N-labeled protein, which constitute the binding interface...
January 24, 2017: Journal of Biomolecular NMR
https://www.readbyqxmd.com/read/27976861/probing-the-energetics-of-dynactin-filament-assembly-and-the-binding-of-cargo-adaptor-proteins-using-molecular-dynamics-simulation-and-electrostatics-based-structural-modeling
#9
Wenjun Zheng
Dynactin, a large multiprotein complex, binds with the cytoplasmic dynein-1 motor and various adaptor proteins to allow recruitment and transportation of cellular cargoes toward the minus end of microtubules. The structure of the dynactin complex is built around an actin-like minifilament with a defined length, which has been visualized in a high-resolution structure of the dynactin filament determined by cryo-electron microscopy (cryo-EM). To understand the energetic basis of dynactin filament assembly, we used molecular dynamics simulation to probe the intersubunit interactions among the actin-like proteins, various capping proteins, and four extended regions of the dynactin shoulder...
December 29, 2016: Biochemistry
https://www.readbyqxmd.com/read/27857681/early-cytoskeletal-protein-modifications-precede-overt-structural-degeneration-in-the-dba-2j-mouse-model-of-glaucoma
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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...
November 1, 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
#17
Małgorzata 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...
November 2016: Genetics
https://www.readbyqxmd.com/read/27668583/evaluation-of-the-dynactin-1-gene-in-leonbergers-and-labrador-retrievers-with-laryngeal-paralysis
#18
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
#19
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
#20
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...
November 2016: Briefings in Bioinformatics
keyword
keyword
96374
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"