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Kinesin

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https://www.readbyqxmd.com/read/28331094/herpes-simplex-virus-ge-gi-and-us9-promote-both-envelopment-and-sorting-of-virus-particles-in-the-cytoplasm-of-neurons-two-processes-that-precede-anterograde-transport-in-axons
#1
Grayson DuRaine, Todd W Wisner, Paul Howard, David C Johnson
Herpes simplex virus (HSV) anterograde transport in neuronal axons is vital, allowing spread from latently-infected ganglia to epithelial tissues where viral progeny are produced in numbers allowing spread to other hosts. HSV membrane proteins gE/gI and US9 initiate the process of anterograde axonal transport ensuring that virus particles are transported from the cytoplasm into the most proximal segments of axons. These proteins do not appear to be important once HSV is inside axons. Previously we described HSV double mutants lacking both gE and US9 that failed to transport virus particles into axons...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28322225/probing-cytoskeletal-modulation-of-passive-and-active-intracellular-dynamics-using-nanobody-functionalized-quantum-dots
#2
Eugene A Katrukha, Marina Mikhaylova, Hugo X van Brakel, Paul M van Bergen En Henegouwen, Anna Akhmanova, Casper C Hoogenraad, Lukas C Kapitein
The cytoplasm is a highly complex and heterogeneous medium that is structured by the cytoskeleton. How local transport depends on the heterogeneous organization and dynamics of F-actin and microtubules is poorly understood. Here we use a novel delivery and functionalization strategy to utilize quantum dots (QDs) as probes for active and passive intracellular transport. Rapid imaging of non-functionalized QDs reveals two populations with a 100-fold difference in diffusion constant, with the faster fraction increasing upon actin depolymerization...
March 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28320970/borc-kinesin-1-ensemble-drives-polarized-transport-of-lysosomes-into-the-axon
#3
Ginny G Farías, Carlos M Guardia, Raffaella De Pace, Dylan J Britt, Juan S Bonifacino
The ability of lysosomes to move within the cytoplasm is important for many cellular functions. This ability is particularly critical in neurons, which comprise vast, highly differentiated domains such as the axon and dendrites. The mechanisms that control lysosome movement in these domains, however, remain poorly understood. Here we show that an ensemble of BORC, Arl8, SKIP, and kinesin-1, previously shown to mediate centrifugal transport of lysosomes in nonneuronal cells, specifically drives lysosome transport into the axon, and not the dendrites, in cultured rat hippocampal neurons...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28319092/the-tdh-gcn5l1-fbxo15-kbp-axis-limits-mitochondrial-biogenesis-in-mouse-embryonic-stem%C3%A2-cells
#4
Valerio Donato, Massimo Bonora, Daniele Simoneschi, Davide Sartini, Yasusei Kudo, Anita Saraf, Laurence Florens, Michael P Washburn, Matthias Stadtfeld, Paolo Pinton, Michele Pagano
Self-renewing naive mouse embryonic stem cells (mESCs) contain few mitochondria, which increase in number and volume at the onset of differentiation. KBP (encoded by Kif1bp) is an interactor of the mitochondrial-associated kinesin Kif1Bα. We found that TDH, responsible for mitochondrial production of acetyl-CoA in mESCs, and the acetyltransferase GCN5L1 cooperate to acetylate Lys501 in KBP, allowing its recognition by and degradation via Fbxo15, an F-box protein transcriptionally controlled by the pluripotency core factors and repressed following differentiation...
March 20, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28318980/cell-specific-%C3%AE-tubulin-isotype-regulates-ciliary-microtubule-ultrastructure-intraflagellar-transport-and-extracellular-vesicle-biology
#5
Malan Silva, Natalia Morsci, Ken C Q Nguyen, Anza Rizvi, Christopher Rongo, David H Hall, Maureen M Barr
Cilia are found on most non-dividing cells in the human body and, when faulty, cause a wide range of pathologies called ciliopathies. Ciliary specialization in form and function is observed throughout the animal kingdom, yet mechanisms generating ciliary diversity are poorly understood. The "tubulin code"-a combination of tubulin isotypes and tubulin post-translational modifications-can generate microtubule diversity. Using C. elegans, we show that α-tubulin isotype TBA-6 sculpts 18 A- and B-tubule singlets from nine ciliary A-B doublet microtubules in cephalic male (CEM) neurons...
March 8, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28314282/comparison-of-the-effects-of-monastrol-and-oxomonastrol-on-human-hepatoma-cell-line-hepg2-c3a
#6
Lilian Areal Marques, Simone Cristine Semprebon, Daniele Sartori, Ângelo DE Fátima, Lúcia Regina Ribeiro, Mário Sérgio Mantovani
Monastrol and its analog oxomonastrol differ by replacement of the sulfur atom present in monastrol to an oxygen atom in oxomonastrol. Monastrol inhibits the mitotic kinesin family member 11 (EG5), which has been studied for its potential use in cancer therapy. The aim of this study was to investigate the effect of monastrol and oxomonastrol on HepG2/C3A cells. Our results showed that monastrol induced DNA damage, reduced cell proliferation, and up-regulated the cytochrome P450 family 1 subfamily A member 1 (CYP1A1) mRNA levels...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28302907/skip-controls-lysosome-positioning-using-a-composite-kinesin-1-heavy-and-light-chain-binding-domain
#7
Anneri Sanger, Yan Y Yip, Thomas S Randall, Stefano Pernigo, Roberto A Steiner, Mark P Dodding
The molecular interplay between cargo recognition and regulation of the activity of the kinesin-1 microtubule motor is not well understood. Using the lysosome adaptor SKIP as model cargo, we show that the heavy chains (KHCs), in addition to the light chains (KLCs), can recognize tryptophan-acidic binding determinants on the cargo when presented in the context of an extended KHC interacting domain. Mutational separation of KHC and KLC binding shows that both interactions are important for SKIP-kinesin-1 interaction in vitro and that KHC binding is important for lysosome transport in vivo...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28300646/developmental-changes-in-trak-mediated-mitochondrial-transport-in-neurons
#8
Omar Loss, F Anne Stephenson
Previous studies established that the kinesin adaptor proteins, TRAK1 and TRAK2, play an important role in mitochondrial transport in neurons. They link mitochondria to kinesin motor proteins via a TRAK acceptor protein in the mitochondrial outer membrane, the Rho GTPase, Miro. TRAKs also associate with enzyme, O-linked N-acetylglucosamine transferase (OGT), to form a quaternary, mitochondrial trafficking complex. A recent report suggested that TRAK1 preferentially controls mitochondrial transport in axons of hippocampal neurons whereas TRAK2 controls mitochondrial transport in dendrites...
March 11, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28300595/a-biophysical-model-of-how-%C3%AE-tubulin-carboxy-terminal-tails-tune-kinesin-1-processivity-along-microtubule
#9
Miljko V Sataric, Dalibor L Sekulic, Slobodan Zdravkovic, Nebojsa M Ralevic
It appears that so-called post-translational modifications of tubulin heterodimers are mostly focussed at positions of amino acid sequences of carboxy-terminal tails. These changes have very profound effects on microtubule functions especially in connection with cellular traffic in terms of motor proteins. In this study, we elaborated the biophysical model aimed to explain the strategy governing these subtle interplays between structural and functional properties of microtubules. We relied onto Langevin equations including fluctuation-dissipation processes...
March 12, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28298410/fus-inclusions-disrupt-rna-localization-by-sequestering-kinesin-1-and-inhibiting-microtubule-detyrosination
#10
Kyota Yasuda, Sarah F Clatterbuck-Soper, Meredith E Jackrel, James Shorter, Stavroula Mili
Cytoplasmic inclusions of the RNA-binding protein fused in sarcoma (FUS) represent one type of membraneless ribonucleoprotein compartment. Formation of FUS inclusions is promoted by amyotrophic lateral sclerosis (ALS)-linked mutations, but the cellular functions affected upon inclusion formation are poorly defined. In this study, we find that FUS inclusions lead to the mislocalization of specific RNAs from fibroblast cell protrusions and neuronal axons. This is mediated by recruitment of kinesin-1 mRNA and protein within FUS inclusions, leading to a loss of detyrosinated glutamate (Glu)-microtubules (MTs; Glu-MTs) and an inability to support the localization of RNAs at protrusions...
March 15, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28298306/il-1%C3%AE-induces-nf-%C3%AE%C2%BAb-and-upregulates-microrna-372-to-inhibit-spinal-cord-injury-recovery
#11
Wei Zhou, Tongzhou Yuan, Youshui Gao, Peipei Yin, Wei Liu, Chenhao Pan, Yingjie Liu, Xiaowei Yu
Excessive inflammation including IL-1β-initiated signaling is among the earlies reactions that can cause neuronal damage following spinal cord injury (SCI). It has been suggested that microRNAs may participate in stem cell repair to facilitate functional recovery after SCI. Here we showed that in cultured human neural stem cells (hNSC) IL-1β reduced the expressions of both KIF3B (kinesin family member 3B) and NOSIP (nitric oxide synthase interacting protein), two key modulators for restricting inflammation and promoting neuronal regeneration...
March 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28291748/the-crystal-structure-of-mouse-lc3b-in-complex-with-the-fyco1-lir-reveals-the-importance-of-the-flanking-region-of-the-lir-motif
#12
Shunya Sakurai, Taisuke Tomita, Toshiyuki Shimizu, Umeharu Ohto
FYVE and coiled-coil domain-containing protein 1 (FYCO1), a multidomain autophagy adaptor protein, mediates microtubule plus-end-directed autophagosome transport by interacting with kinesin motor proteins and with the autophagosomal membrane components microtubule-associated protein 1 light chain 3 (LC3), Rab7 and phosphatidylinositol 3-phosphate (PI3P). To establish the structural basis for the recognition of FYCO1 by LC3, the crystal structure of mouse LC3B in complex with the FYCO1 LC3-interacting region (LIR) motif peptide was determined...
March 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/28290984/kinesin-4-kif21b-is-a-potent-microtubule-pausing-factor
#13
Wilhelmina E van Riel, Ankit Rai, Sarah Bianchi, Eugene A Katrukha, Qingyang Liu, Albert Jr Heck, Casper C Hoogenraad, Michel O Steinmetz, Lukas C Kapitein, Anna Akhmanova
Microtubules are dynamic polymers that in cells can grow, shrink or pause, but the factors that promote pausing are poorly understood. Here, we show that the mammalian kinesin-4 KIF21B is a processive motor that can accumulate at microtubule plus ends and induce pausing. A few KIF21B molecules are sufficient to induce strong growth inhibition of a microtubule plus end in vitro. This property depends on non-motor microtubule-binding domains located in the stalk region and the C-terminal WD40 domain. The WD40-containing KIF21B tail displays preference for a GTP- over a GDP-type microtubule lattice and contributes to the interaction of KIF21B with microtubule plus ends...
March 14, 2017: ELife
https://www.readbyqxmd.com/read/28289130/inhibition-of-ectopic-microtubule-assembly-by-the-kinesin-13-klp-7-mcak-prevents-chromosome-segregation-and-cytokinesis-defects-in-oocytes
#14
Emmanuelle Gigant, Marine Stefanutti, Kimberley Laband, Agata Gluszek-Kustusz, Frances Edwards, Benjamin Lacroix, Gilliane Maton, Julie C Canman, Julie P I Welburn, Julien Dumont
In most species, oocytes lack centrosomes. Accurate meiotic spindle assembly and chromosome segregation -essential to prevent miscarriage or developmental defects- thus occur through atypical mechanisms that are not well characterized. Using quantitative in vitro and in vivo functional assays in the C. elegans oocyte, we provide here novel evidence that the kinesin-13 KLP-7 promotes the destabilization of the whole cellular microtubule network. By counteracting ectopic microtubule assembly and disorganization of the microtubule network, this function is strictly required for spindle organization, chromosome segregation, and cytokinesis in meiotic cells...
March 13, 2017: Development
https://www.readbyqxmd.com/read/28287156/single-molecule-investigation-of-kinesin-1-motility-using-engineered-microtubule-defects
#15
Michael W Gramlich, Leslie Conway, Winnie H Liang, Joelle A Labastide, Stephen J King, Jing Xu, Jennifer L Ross
The structure of the microtubule is tightly regulated in cells via a number of microtubule associated proteins and enzymes. Microtubules accumulate structural defects during polymerization, and defect size can further increase under mechanical stresses. Intriguingly, microtubule defects have been shown to be targeted for removal via severing enzymes or self-repair. The cell's control in defect removal suggests that defects can impact microtubule-based processes, including molecular motor-based intracellular transport...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28284467/moonlighting-motors-kinesin-dynein-and-cell-polarity
#16
REVIEW
Wen Lu, Vladimir I Gelfand
In addition to their well-known role in transporting cargoes in the cytoplasm, microtubule motors organize their own tracks - the microtubules. While this function is mostly studied in the context of cell division, it is essential for microtubule organization and generation of cell polarity in interphase cells. Kinesin-1, the most abundant microtubule motor, plays a role in the initial formation of neurites. This review describes the mechanism of kinesin-1-driven microtubule sliding and discusses its biological significance in neurons...
March 8, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28281683/embedding-dual-function-into-molecular-motors-through-collective-motion
#17
Nen Saito, Kunihiko Kaneko
Protein motors, such as kinesins and dyneins, bind to a microtubule and travel along it in a specific direction. Previously, it was thought that the directionality for a given motor was constant in the absence of an external force. However, the directionality of the kinesin-5 Cin8 was recently found to change as the number of motors that bind to the same microtubule is increased. Here, we introduce a simple mechanical model of a microtubule-sliding assay in which multiple motors interact with the filament. We show that, due to the collective phenomenon, the directionality of the motor changes (e...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28273459/anterograde-transport-of-rab4-associated-vesicles-regulates-synapse-organization-in-drosophila
#18
Swagata Dey, Gary Banker, Krishanu Ray
Local endosomal recycling at synapses is essential to maintain neurotransmission. Rab4GTPase, found on sorting endosomes, is proposed to balance the flow of vesicles among endocytic, recycling, and degradative pathways in the presynaptic compartment. Here, we report that Rab4-associated vesicles move bidirectionally in Drosophila axons but with an anterograde bias, resulting in their moderate enrichment at the synaptic region of the larval ventral ganglion. Results from FK506 binding protein (FKBP) and FKBP-Rapamycin binding domain (FRB) conjugation assays in rat embryonic fibroblasts together with genetic analyses in Drosophila indicate that an association with Kinesin-2 (mediated by the tail domain of Kinesin-2α/KIF3A/KLP64D subunit) moves Rab4-associated vesicles toward the synapse...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28267922/tetrazine-trans-cyclooctene-mediated-conjugation-of-antibodies-to-microtubules-facilitates-subpicomolar-protein-detection
#19
Samata Chaudhuri, Till Korten, Stefan Diez
Engineering cargo-loading strategies is crucial to developing nanotechnological applications of microtubule-based biomolecular transport systems. Here, we report a highly efficient and robust bioconjugation scheme to load antibodies to microtubules. Our method takes advantage of the inverse-electron-demand Diels-Alder addition reaction between tetrazine and trans-cyclooctene: the fastest known bioorthogonal reaction, characterized by its excellent selectivity and biocompatibility. As proof of concept, we performed kinesin-1 gliding motility assays with antibody-conjugated microtubules and demonstrated the highly sensitive detection of fluorescent protein analyte down to 0...
March 14, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28267259/the-axonal-transport-motor-kinesin-2-navigates-microtubule-obstacles-via-protofilament-switching
#20
Gregory J Hoeprich, Keith J Mickolajczyk, Shane R Nelson, William O Hancock, Christopher L Berger
Axonal transport involves kinesin motors trafficking cargo along microtubules that are rich in microtubule-associated proteins (MAPs). Much attention has focused on the behavior of kinesin-1 in the presence of MAPs, which has overshadowed understanding the contribution of other kinesins such as kinesin-2 in axonal transport. We have previously shown that, unlike kinesin-1, kinesin-2 in vitro motility is insensitive to the neuronal MAP Tau. However, the mechanism by which kinesin-2 efficiently navigates Tau on the microtubule surface is unknown...
March 7, 2017: Traffic
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