Abstract
It was recently noticed that in vitro motility assays, driven by random distributed dynein c, microtubules could form self-organized circular patterns, which could be of importance to the design of nanobiomechanical machines. In order to determine key parameters that control the self-organized movem...
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PMID: 19508056
PDF is available here.
Abstract
We live-imaged movements of GFP-tagged mitochondria in larval Drosophila motor axons upon genetic manipulations of Miro. Loss of Drosophila Miro (dMiro) reduced the effectiveness of both anterograde and retrograde mitochondrial transport by selectively impairing kinesin- or dynein-mediated movements...
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PMID: 19403812
PDF is available here.
Abstract
We report that microtubule (MT) nucleation at the Golgi apparatus requires AKAP450, a centrosomal gamma-TuRC-interacting protein that also forms a distinct network associated with the Golgi. Depletion of AKAP450 abolished MT nucleation at the Golgi, whereas depletion of the cis-Golgi protein GM130 l...
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PMID: 19242490
PDF is available here.
Abstract
We show that human cells depleted of dynein light intermediate chain 1 (LIC1) delay in metaphase with increased interkinetochore distances; dynein remains intact, localised and functional. The checkpoint proteins Mad1/2 and Zw10 localise to kinetochores under full tension, whereas BubR1 is diminishe...
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PMID: 19229290
PDF is available here.
Abstract
We report that the stalk shaft of rat cytoplasmic dynein is an antiparallel alpha-helical coiled coil, the stability of which is markedly altered by changes at its proximal and distal ends, consistent with a structure capable of rapid, cyclical rearrangement during the dynein cross-bridge cycle....
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PMID: 19222235
PDF is available here.
Abstract
We show that changes in registration between the two helices of the coiled coil can perform this function. We locked the coiled coil at three specific registrations using oxidation to disulfides of paired cysteine residues introduced into the two helices. These trapped ATPase activity either in a mi...
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PMID: 19198589
PDF is available here.
Abstract
We previously observed that high-risk human papillomavirus type 16 (HPV16) E7 expression leads to the delocalization of dynein from mitotic spindles (C. L. Nguyen, M. E. McLaughlin-Drubin, and K. Munger, Cancer Res. 68:8715-8722, 2008). Here, we show that HPV16 E7 associates with nuclear mitotic app...
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PMID: 19052088
PDF is available here.
Abstract
These results suggest that calaxin is a potential Ca(2+)-dependent modulator of outer arm dynein in metazoan cilia and flagella....
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PMID: 18620543
PDF is available here.
Abstract
We show that CHIP has a previously unexpected critical role in the aggresome pathway. CHIP interacts with iNOS and promotes its ubiquitination and degradation by the proteasome as well as its sequestration to the aggresome. CHIP-mediated iNOS targeting to the proteasome sequentially precedes CHIP-me...
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PMID: 18955503
PDF is available here.
Abstract
Here, we present the comparative genomic analysis of the motor protein repertoire of 21 completely sequenced arthropod species using the owl limpet Lottia gigantea as outgroup. Arthropods contain up to 17 myosins grouped into 13 classes. The myosins are in almost all cases clear paralogs, and thus t...
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PMID: 19383156
PDF is available here.
Abstract
We show that the SynA synaptobrevin endocytic recycling cargo traffics through this region, which strongly supports the contention that polarized hyphal growth involves the association of endocytic recycling with the plus ends of MTs located at the tip, near the endocytic internalization collar....
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PMID: 19000168
PDF is available here.
Abstract
The present study investigated the distribution of cytoplasmic dynein, dynactin and 20S proteasomes in oocytes isolated from small (<2 mm) and large (2-8 mm) follicles during IVM. Immediately after chromatin condensation (germinal vesicle (GV) breakdown), dynactin was closely associated with the chr...
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PMID: 19210921
PDF is available here.
Abstract
We show that upon depletion of the minus-end-directed motor dynein, or the dynein-binding protein Lis1, bipolar spindles can form in human cells with substantially less Eg5 activity, suggesting that dynein and Lis1 produce an inward force that counteracts the Eg5-dependent outward force. Interesting...
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PMID: 19020519
PDF is available here.
Abstract
We present the clearest views so far of stalks in action, by observing sea urchin, outer arm dynein molecules bound to microtubules, with a new method, "cryo-positive stain" electron microscopy. The dynein molecules in the complex were shown to be active in in vitro motility assays. Analysis of the...
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PMID: 19064920
PDF is available here.
Abstract
We performed the matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis followed by immunoprecipitation. We confirmed that DUB-1 interacts with dynein heavy chain, which is known to regulate the movement of organelles and microtubule binding ability. In...
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PMID: 18980247
PDF is available here.
Abstract
We report the crystal structure of the mouse cytoplasmic dynein MTBD and a portion of the coiled coil, which supports a mechanism by which the ATPase domain and MTBD may communicate through a shift in the heptad registry of the coiled coil. Surprisingly, functional data suggest that the MTBD, and no...
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PMID: 19074350
PDF is available here.
Abstract
We rigorously test these notions using lipid droplets in Drosophila embryos. We first employ antibody inhibition, genetics, biochemistry, and particle tracking to demonstrate that kinesin-1 mediates plus-end droplet motion. We then measure how variation in kinesin-1 expression affects the forces dri...
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PMID: 19070579
PDF is available here.
Heymut Omran,
Daisuke Kobayashi,
Heike Olbrich,
Tatsuya Tsukahara,
Niki T Loges,
Haruo Hagiwara,
Qi Zhang,
Gerard Leblond,
Eileen O'Toole,
Chikako Hara,
Hideaki Mizuno,
Hiroyuki Kawano,
Manfred Fliegauf,
Toshiki Yagi,
Sumito Koshida,
Atsushi Miyawaki,
Hanswalter Zentgraf,
Horst Seithe,
Richard Reinhardt,
Yoshinori Watanabe,
Ritsu Kamiya,
David R Mitchell and
Hiroyuki Takeda
Abstract
We report a new gene, kintoun (ktu), involved in this cytoplasmic process. This gene was first identified in a medaka mutant, and found to be mutated in primary ciliary dyskinesia patients from two affected families as well as in the pf13 mutant of Chlamydomonas. In the absence of Ktu/PF13, both out...
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PMID: 19052621
PDF is available here.
Abstract
Cytoplasmic dynein functions at several sites during mitosis; however, the basis of targeting to each site remains unclear. Tandem mass spectrometry analysis of mitotic dynein revealed a phosphorylation site in the dynein intermediate chains (ICs) that mediates binding to kinetochores. IC phosphoryl...
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PMID: 19029334
PDF is available here.
Abstract
We used cryo-electron tomography to reconstruct the three-dimensional structure of inner dynein arms from Chlamydomonas reinhardtii. All the eight different heavy chains were identified in one 96-nm periodic repeat, as expected from previous biochemical studies. Based on mutants, we identified the p...
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PMID: 19029338
PDF is available here.
Abstract
We report on the relationship between the polarity kinase MARK2/Par-1 and its substrate, the well-known lissencephaly-associated gene doublecortin (DCX), during cortical radial migration. We have previously shown using in utero electroporation that reduced MARK2 levels resulted in multipolar neurons...
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PMID: 19036994
PDF is available here.
Abstract
We show that the centrosome recruitment of parkin was mediated by its direct binding to HDAC6 through multiple interaction domains. The tubulin deacetylase activity of HDAC6 was required for the accumulation of parkin as well as its dispersion upon the reversal of proteasome inhibition. The bidirect...
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PMID: 19036992
PDF is available here.
Abstract
We have identified alternatively spliced isoforms of p150Glued that are expressed in a tissue-specific manner and which differ significantly in their affinity for microtubules. Live cell assays indicate that these alternatively spliced isoforms also differ significantly in their microtubule plus end...
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PMID: 18812314
PDF is available here.
Abstract
We show that HPV16 E7 expression leads to an increased population of mitotic cells with dynein delocalized from the mitotic spindle. This function maps to sequences of HPV16 E7 that are distinct from the region necessary for centrosome overduplication. However, contrary to previous reports, we provi...
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PMID: 18974113
PDF is available here.
Niki Tomas Loges,
Heike Olbrich,
Lale Fenske,
Huda Mussaffi,
Judit Horvath,
Manfred Fliegauf,
Heiner Kuhl,
Gyorgy Baktai,
Erzsebet Peterffy,
Rahul Chodhari,
Eddie M K Chung,
Andrew Rutman,
Christopher O'Callaghan,
Hannah Blau,
Laszlo Tiszlavicz,
Katarzyna Voelkel,
Michal Witt,
Ewa Zietkiewicz,
Juergen Neesen,
Richard Reinhardt,
Hannah M Mitchison and
Heymut Omran
Abstract
We identified homozygous loss-of-function DNAI2 mutations (IVS11+1G > A) in four individuals from a family with PCD and ODA defects. Further mutational screening of 105 unrelated PCD families detected two distinct homozygous mutations, including a nonsense (c.787C > T) and a splicing mutation (IVS3-...
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PMID: 18950741
PDF is available here.
Abstract
Most patients presented with chronic respiratory tract infections or infertility. Dynein arm defects, transposition defects, and radial spoke defects were the most commonly encountered abnormal findings. Less-frequent abnormal findings included compound cilia, supernumerary microtubules, and dense g...
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PMID: 18976016
PDF is available here.
Abstract
We investigated the guanidine induced unfolding transition of dynein light chain protein (DLC8), a cargo adaptor of the dynein complex in the pH range 7-10. It is observed that while the protein remains a dimer in the entire pH range, its stability is somewhat reduced at alkaline pH. Global unfoldin...
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PMID: 18692162
PDF is available here.
Abstract
We report our characterization of the LIC in Drosophila. Unlike vertebrates, in which two Lic genes encode multiple subunit isoforms, the Drosophila LIC is encoded by a single gene. We determined that the single LIC polypeptide is phosphorylated, and that different phosphoisoforms can assemble into...
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PMID: 18799620
PDF is available here.
Abstract
We show that dynein extracted from wild-type axonemes can rebind to oda16 axonemes in vitro, and dynein in oda16 cytoplasmic extracts can bind to docking sites on pf28 (oda) axonemes, which is consistent with a role for ODA16 in dynein transport, rather than subunit preassembly or binding site forma...
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PMID: 18852297
PDF is available here.
Masami Yamada,
Shiori Toba,
Yuko Yoshida,
Koji Haratani,
Daisuke Mori,
Yoshihisa Yano,
Yuko Mimori-Kiyosue,
Takeshi Nakamura,
Kyoko Itoh,
Shinji Fushiki,
Mitsutoshi Setou,
Anthony Wynshaw-Boris,
Takayuki Torisawa,
Yoko Y Toyoshima and
Shinji Hirotsune
Abstract
We demonstrate that LIS1 suppresses the motility of cytoplasmic dynein on microtubules (MTs), whereas NDEL1 releases the blocking effect of LIS1 on cytoplasmic dynein. We demonstrate that LIS1, cytoplasmic dynein and MT fragments co-migrate anterogradely. When LIS1 function was suppressed by a block...
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PMID: 18784752
PDF is available here.
Abstract
Individual neurons form specific elaborate dendritic structures that receive presynaptic information. The pattern of dendritic branching is regulated by the microtubule-associated motor protein dynein, which is responsible for the transport of essential endosomes and other organelles into the dendri...
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PMID: 18830220
PDF is available here.
Abstract
We show that the microtubule motor dynein has a crucial role in polarized transport and in controlling the orientation of axonal microtubules in Drosophila melanogaster dendritic arborization (da) neurons. Changes in organelle distribution within the dendritic arbors of dynein mutant neurons correla...
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PMID: 18758451
PDF is available here.
Abstract
We show that in utero gene transfer of Atoh1 produces functional supernumerary hair cells in the mouse cochlea. The induced hair cells display stereociliary bundles, attract neuronal processes and express the ribbon synapse marker carboxy-terminal binding protein 2 (refs 12,13). Moreover, the hair c...
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PMID: 18754012
PDF is available here.
Abstract
We expressed a series of dynein tail fragments, which we find displace motor-containing dynein heavy chain (HC) from kinetochores without affecting other subunits, regulatory factors, or microtubule binding proteins. Cells with bipolar mitotic spindles progress to late prometaphase-metaphase at norm...
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PMID: 18809721
PDF is available here.
Abstract
We report here that Lis1 and Ndel1 reduction in a mitotic cell line impairs prophase nuclear envelope (NE) invagination (PNEI). This dynein-dependent process facilitates NE breakdown (NEBD) and occurs before the establishment of the bipolar spindle. Ndel1 phosphorylation is important for this functi...
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PMID: 18809722
PDF is available here.
Abstract
We have generated transgenic mice with neuron-specific expression of Bicaudal D2 N-terminus (BICD2-N) to chronically impair dynein/dynactin function. Motor neurons expressing BICD2-N showed accumulation of dynein and dynactin in the cell body, Golgi fragmentation and several signs of impaired retrog...
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PMID: 18579581
PDF is available here.
Abstract
We have analyzed the single molecule motility properties of yeast cytoplasmic dynein mutants bearing mutations that prevent ATP hydrolysis at AAA3 or AAA4. Both mutants remain processive, but the AAA4 mutant exhibits a surprising increase in processivity due to its tighter affinity for microtubules....
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PMID: 18650442
PDF is available here.
Abstract
We clarified the effects of USH1B mutations on human myosin VIIa motor function for the first time. The missense mutations of USH1B significantly inhibited the actin activation of ATPase activity of myosin VIIa. G25R, R212C, A397D, and E450Q mutations abolished the actin-activated ATPase activity co...
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PMID: 18700726
PDF is available here.
Abstract
We have studied the role of the dynein-dynactin complex, a microtubule-based molecular motor, in the process of T cell activation during T cell antigen-presenting cell cognate immune interactions. Impairment of dynein-dynactin complex activity, either by overexpressing the p50-dynamitin component of...
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PMID: 18779373
PDF is available here.
Abstract
We confirm that Kar3p is required for nuclear congression in mating but that neither Kar3p nor the dynein motor protein Dyn1p is required for nuclear migration in the mating projection prior to cell fusion. In addition, we show that C. albicans Kar3p plays an important role in the cell and colony mo...
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PMID: 18586948
PDF is available here.
Abstract
Anterograde transport of brain-derived neurotrophic factor (BDNF) vesicles from the soma to neurite terminals is necessary for activity-dependent secretion of BDNF to mediate synaptic plasticity, memory and learning, and retrograde BDNF transport back to the soma for recycling. In our study, overexp...
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PMID: 18573344
PDF is available here.
Abstract
These results suggest that LC8 may dissociate from the 320-kDa nNOSalpha dimer upon binding to membrane, thus supporting the view that LC8 may transport nNOSalpha dimer to the varicosity membrane for participation in nitrergic neurotransmission....
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PMID: 18635601
PDF is available here.
Abstract
We demonstrate bidirectional nanotransport by integrating kinesin and dynein motor proteins. Our molecular system allows microtubule orientation of either polarity in a microfluidic channel to construct a transport track. Each motor protein acts as a nanoactuators that transports microspheres in opp...
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PMID: 18646216
PDF is available here.
Reto Gassmann,
Anthony Essex,
Jia-Sheng Hu,
Paul S Maddox,
Fumio Motegi,
Asako Sugimoto,
Sean M O'Rourke,
Bruce Bowerman,
Ian McLeod,
John R Yates,
Karen Oegema,
Iain M Cheeseman and
Arshad Desai
Abstract
We use the Caenorhabditis elegans embryo to investigate the function of kinetochore dynein by analyzing the Rod/Zwilch/Zw10 (RZZ) complex and the associated coiled-coil protein SPDL-1. Both components are essential for Mad2 targeting to kinetochores and spindle checkpoint activation. RZZ complex inh...
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PMID: 18765790
PDF is available here.
Abstract
The attachment of chromosomes to spindle microtubules during mitosis is a delicate and intricate process on which eukaryotic cells critically depend to maintain their ploidy. In this issue of Genes & Development, Gassmann and colleagues (pp. 2385-2399 present an analysis of the recently discovered S...
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PMID: 18765786
PDF is available here.
Abstract
We selected a partial cDNA fragment by differential display reverse-transcription PCR using total RNA extracted from 5-day-old and 10-day-old mouse ovaries, and its open reading frame was obtained by rapid amplification of cDNA ends. Sequencing showed that the fragment is the mouse dynein axonemal i...
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PMID: 18547164
PDF is available here.
Abstract
We developed an experimental system using elastase-treated axonemes of sperm flagella, which have a large Ca(2+)-induced principal bend (P-bend) at the base. On photoreleasing ATP from caged ATP, they slid apart into two bundles of doublets. When the distal overlap region of the slid bundles was ben...
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PMID: 18682495
PDF is available here.
Abstract
Dominant mutations in cytoplasmic dynein (Loa or Cra) have been reported to provoke selective, age-dependent killing of motor neurons, while paradoxically slowing degeneration and death of motor neurons in one mouse model of an inherited form of ALS. Examination of Loa animals reveals no degeneratio...
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PMID: 18719118
PDF is available here.
Abstract
We measure mitotic motor movement inside a dynamic spindle. We find that dynein-dynactin transports the essential motor Eg5 toward the spindle poles in Xenopus laevis egg extract spindles, revealing a direct interplay between two motors of opposite directionality. This transport occurs throughout th...
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PMID: 18710923
PDF is available here.
Abstract
We use quantitative fluorescent speckle microscopy to map with high resolution the spatial organization of microtubule flux in Xenopus laevis egg extract meiotic spindles. We find that the flux velocity decreases near spindle poles by approximately 20%. The regional variation is independent of funct...
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PMID: 18710922
PDF is available here.
Abstract
We recently showed that a novel disulfide reductase, TRP14, inhibits tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation, and we identified the dynein light chain LC8, which interacts with the NF-kappaB inhibitor IkappaBalpha, as a potential substrate of TRP14. We now show the molecu...
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PMID: 18579519
PDF is available here.
Abstract
We apply them to proteins. Dyneins are important proteins of these parasites governing fundamental processes such as cilia and flagella motion, nuclear migration, organization of the mitotic splinde, and chromosome separation during mitosis. However, despite the interest for them as potential drug t...
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PMID: 18662882
PDF is available here.
Abstract
We identified Star in a screen designed to recover second-site modifiers of the dominant rough eye phenotype of the Glued mutation Gl(1). The Glued (Gl) locus encodes the p150 subunit of the dynactin complex, an activator of cytoplasmic dynein-driven motility. We show that alleles of Gl and dynein g...
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PMID: 18653542
PDF is available here.
Abstract
We report for the first time a possible association between mutations in dynein genes and isolated AZS. Male carriers of the mutations always exhibit AZS, whereas female carriers manifest no alterations in either fertility or pulmonary clearance....
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PMID: 18492703
PDF is available here.
Abstract
We demonstrate that LD redistribution requires only core protein and is accompanied by reduced abundance of adipocyte differentiation-related protein (ADRP) on LD surfaces. Using small hairpin RNA technology, we show that knock down of ADRP has a similar phenotypic effect on LD redistribution. Hence...
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PMID: 18489704
PDF is available here.
Abstract
We reinvestigated the interaction between ZW10 and dynamitin, and showed that the N-terminal region of ZW10 is the major binding site for dynamitin and, like full-length ZW10, could potentially move along microtubules to the centrosomal area in a dynein-dynactin-dependent manner. Competitive binding...
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PMID: 18782227
PDF is available here.