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https://www.readbyqxmd.com/read/28436967/microtubule-minus-end-regulation-at-spindle-poles-by-an-aspm-katanin-complex
#1
Kai Jiang, Lenka Rezabkova, Shasha Hua, Qingyang Liu, Guido Capitani, A F Maarten Altelaar, Albert J R Heck, Richard A Kammerer, Michel O Steinmetz, Anna Akhmanova
ASPM (known as Asp in fly and ASPM-1 in worm) is a microcephaly-associated protein family that regulates spindle architecture, but the underlying mechanism is poorly understood. Here, we show that ASPM forms a complex with another protein linked to microcephaly, the microtubule-severing ATPase katanin. ASPM and katanin localize to spindle poles in a mutually dependent manner and regulate spindle flux. X-ray crystallography revealed that the heterodimer formed by the N- and C-terminal domains of the katanin subunits p60 and p80, respectively, binds conserved motifs in ASPM...
April 24, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28435525/development-and-biological-evaluation-of-a-photoactivatable-small-molecule-microtubule-targeting-agent
#2
Alexander Döbber, Athena F Phoa, Ramzi H Abbassi, Brett W Stringer, Bryan W Day, Terrance G Johns, Mohammed Abadleh, Christian Peifer, Lenka Munoz
Photoremovable protecting groups added to bioactive molecules provide spatial and temporal control of the biological effects. We present synthesis and characterization of the first photoactivatable small-molecule tubulin inhibitor. By blocking the pharmacophoric OH group on compound 1 with photoremovable 4,5-dimethoxy-2-nitrobenzyl moiety we developed the photocaged prodrug 2 that had no effect in biological assays. Short UV light exposure of the derivative 2 or UV-irradiation of cells treated with 2 resulted in fast and potent inhibition of tubulin polymerization, attenuation of cell viability, and apoptotic cell death, implicating release of the parent active compound...
April 13, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28434791/neuronal-cells-derived-from-human-induced-pluripotent-stem-cells-as-a-functional-tool-of-melanocortin-system
#3
Nobuko Yamada-Goto, Yukari Ochi, Goro Katsuura, Yui Yamashita, Ken Ebihara, Michio Noguchi, Junji Fujikura, Daisuke Taura, Masakatsu Sone, Kiminori Hosoda, Paul E Gottschall, Kazuwa Nakao
BACKGROUND: The preparation of human neurons derived from human induced pluripotent stem (iPS) cells can serve as a potential tool for evaluating the physiological and pathophysiological properties of human neurons and for drug development. METHODS: In the present study, the functional activity in neuronal cells differentiated from human iPS cells was observed. RESULTS: The differentiated cells expressed mRNAs for classical neuronal markers (microtubule-associated protein 2, β-tubulin III, calbindin 1, synaptophysin and postsynaptic density protein 95) and for subunits of various excitatory and inhibitory transmitters (NR1, NR2A, NR2B, GABAA α1)...
April 7, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28433664/ovaries-of-the-white-worm-enchytraeus-albidus-annelida-clitellata-are-composed-of-16-celled-meroistic-germ-line-cysts
#4
Anna Z Urbisz, Łukasz Chajec, Agnieszka Brąszewska-Zalewska, Janusz Kubrakiewicz, Piotr Świątek
The paired ovaries of E. albidus are like a bunch of grapes and are composed of clearly separated units, syncytial germ cysts (clusters), which are surrounded by a thin layer of somatic cells. Each cyst maintains the connection with the ovary by an extended stalk that is composed of somatic cells. The spatial architecture of the germ-line cysts found in E. albidus is the same as in other clitellate annelids that have been studied to date. As a rule, germ cells are located at the cyst periphery and each has only one ring canal that connects it to the common and centrally located cytoplasmic mass, the cytophore...
April 19, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28433567/ppar-%C3%AE-agonist-rosiglitazone-reduces-autophagy-and-promotes-functional-recovery-in-experimental-traumaticspinal-cord-injury
#5
Hongpeng Li, Qin Zhang, Xiaohui Yang, Liping Wang
BACKGROUND: Secondary damage is often more important in determining the functional outcome and provides a practical target for therapeutic intervention. Rosiglitazone (ROSG) is a potent PPAR-γ agonist and has been shown to induce neuroprotection in animal models of spinal cord injury (SCI). However, it is still unclear whether this PPAR-γ agonist can mediate neuronal autophagy after SCI. METHODS: SCI was induced by application of vascular clips (force of 24g) to the dura via a four-level T5-T8 laminectomy...
April 19, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28433513/ortho-group-activation-of-a-bromopyrrole-ester-in-suzuki-miyaura-cross-coupling-reactions-application-to-the-synthesis-of-new-microtubule-depolymerizing-agents-with-potent-cytotoxic-activities
#6
John T Gupton, Scott Yeudall, Nakul Telang, Megan Hoerrner, Ellis Huff, Evan Crawford, Katie Lounsbury, Michael Kimmel, William Curry, Andrew Harrison, Wen Juekun, Alex Shimozono, Joe Ortolani, Kristin Lescalleet, Jon Patteson, Veronica Moore-Stoll, Cristina C Rohena, Susan L Mooberry, Ahmad J Obaidullah, Glen E Kellogg, James A Sikorski
New microtubule depolymerizing agents with potent cytotoxic activities have been prepared with a 5-cyano or 5-oximino group attached to a pyrrole core. The utilization of ortho activation of a bromopyrrole ester to facilitate successful Suzuki-Miyaura cross-coupling reactions was a key aspect of the synthetic methodology. This strategy allows for control of regiochemistry with the attachment of four completely different groups at the 2, 3, 4 and 5 positions of the pyrrole scaffold. Biological evaluations and molecular modeling studies are reported for these examples...
April 11, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28433265/high-pressure-microscopy-for-tracking-dynamic-properties-of-molecular-machines
#7
Masayoshi Nishiyama
High-pressure microscopy is one of the powerful techniques to visualize the effects of hydrostatic pressures on research targets. It could be used for monitoring the pressure-induced changes in the structure and function of molecular machines in vitro and in vivo. This review focuses on the dynamic properties of the assemblies and machines, analyzed by means of high-pressure microscopy measurement. We developed a high-pressure microscope that is optimized both for the best image formation and for the stability to hydrostatic pressure up to 150 MPa...
March 30, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28433077/development-and-clinical-utility-of-a-blood-based-test-service-for-the-rapid-identification-of-actionable-mutations-in-non-small-cell-lung-carcinoma
#8
Hestia Mellert, Trudi Foreman, Leisa Jackson, Dianna Maar, Scott Thurston, Kristina Koch, Amanda Weaver, Samantha Cooper, Nicholas Dupuis, Ubaradka G Sathyanarayana, Jakkie Greer, Westen Hahn, Dawne Shelton, Paula Stonemetz, Gary A Pestano
Nearly 80% of cancer patients do not have genetic mutation results available at initial oncology consultation; up to 25% of patients begin treatment before receiving their results. These factors hinder the ability to pursue optimal treatment strategies. This study validates a blood-based genome-testing service that provides accurate results within 72 hours. We focused on targetable variants in advanced non-small cell lung carcinoma-epidermal growth factor receptor gene (EGFR) variant L858R, exon 19 deletion (ΔE746-A750), and T790M; GTPase Kirsten ras gene (KRAS) variants G12C/D/V; and echinoderm microtubule associated protein like and 4 anaplastic lymphoma receptor tyrosine kinase fusion (EML4-ALK) transcripts 1/2/3...
May 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28432921/gates-for-soluble-and-membrane-proteins-and-two-trafficking-systems-ift-and-lift-establish-a-dynamic-ciliary-signaling-compartment
#9
REVIEW
Victor L Jensen, Michel R Leroux
Primary cilia are microtubule-based organelles found on most mammalian cell surfaces. They possess a soluble matrix and membrane contiguous with the cell body cytosol and plasma membrane, and yet, have distinct compositions that can be modulated to enable dynamic signal transduction. Here, we discuss how specialized ciliary compartments are established using a coordinated network of gating, trafficking and targeting activities. Cilium homeostasis is maintained by a size-selective molecular mesh that limits soluble protein entry, and by a membrane diffusion barrier localized at the transition zone...
April 19, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28432787/presynaptic-morphology-and-vesicular-composition-determine-vesicle-dynamics-in-mouse-central-synapses
#10
Laurent Guillaud, Dimitar Dimitrov, Tomoyuki Takahashi
Transport of synaptic vesicles (SVs) in nerve terminals is thought to play essential roles in maintenance of neurotransmission. To identify factors modulating SV movements, we performed real-time imaging analysis of fluorescently labeled SVs in giant calyceal and conventional hippocampal terminals. Compared with small hippocampal terminals, SV movements in giant calyceal terminals were faster, longer and kinetically more heterogeneous. Morphological maturation of giant calyceal terminals was associated with an overall reduction in SV mobility and displacement heterogeneity...
April 22, 2017: ELife
https://www.readbyqxmd.com/read/28432079/regulation-of-microtubule-associated-motors-drives-intermediate-filament-network-polarization
#11
Cécile Leduc, Sandrine Etienne-Manneville
Intermediate filaments (IFs) are key players in the control of cell morphology and structure as well as in active processes such as cell polarization, migration, and mechanoresponses. However, the regulatory mechanisms controlling IF dynamics and organization in motile cells are still poorly understood. In this study, we investigate the mechanisms leading to the polarized rearrangement of the IF network along the polarity axis. Using photobleaching and photoconversion experiments in glial cells expressing vimentin, glial fibrillary acidic protein, and nestin, we show that the distribution of cytoplasmic IFs results from a continuous turnover based on the cooperation of an actin-dependent retrograde flow and anterograde and retrograde microtubule-dependent transports...
April 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28431939/modulation-of-hat-activity-by-the-brca2n372hvariation-is-a-novel-mechanism-of-paclitaxel-resistance-in-breast-cancer-cell-lines
#12
Woo Sun Kwon, Sun Young Rha, Hei-Cheul Jeung, Tae Soo Kim, Hyun Cheol Chung
Paclitaxel stabilizes microtubule polymerization, enhances microtubule assembly, andG2/M arrests, leading to cell death. Paclitaxel resistance has been attributed to a variety of mechanisms. In the present study, we define a new resistance mechanism to paclitaxel based onBRCA2variation. Chemo-sensitivity to paclitaxel based on the variations was compared. Restoration of paclitaxel sensitivity was induced indirectly with combined treatment of paclitaxel and HDAC inhibitor. Variant and wild type of BRCA2 clones were obtained from wild and variant cells, respectively...
April 18, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28431332/sperm-morphology-of-the-leafhopper-diaphorina-citri-kuwayama-hemiptera-sternorrhyncha-psylloidea-liviidae
#13
Marcelo Silva Barcellos, Jamile Fernanda Silva Cossolin, Glenda Dias, José Lino-Neto
In this study, by using light and electron microscopy, we describe the sperm morphology of the leafhopper Diaphorina citri, a serious pest of citrus throughout the world. In this species the sperm measures 538.49±8.75μm in length, and as observed in psylloids, the sperm, when manipulated, opens into two filaments, one of which is attached to the nuclear base and the other becomes free. Along the flagellum, and only of it, there are lateral projections, about 2μm in length. Furthermore, at the end of the flagellum three appendages, with approximately 7μm in length, are observed...
April 8, 2017: Micron: the International Research and Review Journal for Microscopy
https://www.readbyqxmd.com/read/28431155/motoring-through-the-role-of-kinesin-superfamily-proteins-in-female-meiosis
#14
Nicole J Camlin, Eileen A McLaughlin, Janet E Holt
BACKGROUND: The kinesin motor protein family consists of 14 distinct subclasses and 45 kinesin proteins in humans. A large number of these proteins, or their orthologues, have been shown to possess essential function(s) in both the mitotic and the meiotic cell cycle. Kinesins have important roles in chromosome separation, microtubule dynamics, spindle formation, cytokinesis and cell cycle progression. This article contains a review of the literature with respect to the role of kinesin motor proteins in female meiosis in model species...
April 18, 2017: Human Reproduction Update
https://www.readbyqxmd.com/read/28430876/ift25-an-intraflagellar-transporter-protein-dispensable-for-ciliogenesis-in-somatic-cells-is-essential-for-sperm-flagella-formation
#15
Hong Liu, Wei Li, Yong Zhang, Zhengang Zhang, Xuejun Shang, Ling Zhang, Shiyang Zhang, Yanwei Li, Andres V Somoza, Brandon Delpi, George L Gerton, James A Foster, Rex A Hess, Gregory J Pazour, Zhibing Zhang
Intraflagellar transport (IFT) is a conserved mechanism essential for the assembly and maintenance of most eukaryotic cilia and flagella. However, IFT25, a component of the IFT complex is not required for the formation of cilia in somatic tissues. In mice, the gene is highly expressed in the testis, and its expression is up-regulated during the final phase when sperm flagella are formed. To investigate the role of IFT25 in sperm flagella formation, the gene was specifically disrupted in male germ cells. All homozygous knockout mice survived to adulthood and did not show any gross abnormalities...
April 18, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28430595/minus-end-directed-kinesin-14-kifc1-regulates-the-positioning-and-architecture-of-the-golgi-apparatus
#16
Zhen-Yu She, Meng-Ying Pan, Fu-Qing Tan, Wan-Xi Yang
The Golgi apparatus is the central organelle along the eukaryotic secretory and endocytic pathway. In non-polarized mammalian cells, the Golgi complex is usually located proximal to the nucleus at the cell center and is closely associated with the microtubule organizing center. Microtubule networks are essential in the organization and central localization of the Golgi apparatus, but the molecular basis underlying these processes are poorly understood. Here we reveal that minus end-directed kinesin-14 KIFC1 proteins are required for the structural integrity and positioning of the Golgi complex in non-polarized mammalian cells...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430047/arf-gaps-and-molecular-motors
#17
Ruibai Luo, Christine E Reed, Jeffrey A Sload, Linda Wordeman, Paul A Randazzo, Pei-Wen Chen
Arf GTPase-activating proteins (Arf GAPs) were first identified as regulators of the small GTP-binding proteins ADP-ribosylation factors (Arfs). The Arf GAPs are a large family of proteins in metazoans, outnumbering the Arfs that they regulate. The members of the Arf GAP family have complex domain structures and some have been implicated in particular cellular functions, such as cell migration, or with particular pathologies, such as tumor invasion and metastasis. The specific effects of Arfs sometimes depend on the Arf GAP involved in their regulation...
April 21, 2017: Small GTPases
https://www.readbyqxmd.com/read/28429652/atypical-regulators-of-wnt-%C3%AE-catenin-signaling-as-potential-therapeutic-targets-in-hepatocellular-carcinoma
#18
Jianxiang Chen, Muthukumar Rajasekaran, Kam M Hui
Hepatocellular carcinoma is one of the most common causes of cancer-related death worldwide. Hepatocellular carcinoma development depends on the inhibition and activation of multiple vital pathways, including the Wnt signaling pathway. The Wnt/β-catenin pathway lies at the center of various signaling pathways that regulate embryonic development, tissue homeostasis and cancers. Activation of the Wnt/β-catenin pathway has been observed frequently in hepatocellular carcinoma. However, activating mutations in β-catenin, Axin and Adenomatous Polyposis Coli only contribute to a portion of the Wnt signaling hyper-activation observed in hepatocellular carcinoma...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28428427/microtubules-acquire-resistance-from-mechanical-breakage-through-intralumenal-acetylation
#19
Zhenjie Xu, Laura Schaedel, Didier Portran, Andrea Aguilar, Jérémie Gaillard, M Peter Marinkovich, Manuel Théry, Maxence V Nachury
Eukaryotic cells rely on long-lived microtubules for intracellular transport and as compression-bearing elements. We considered that long-lived microtubules are acetylated inside their lumen and that microtubule acetylation may modify microtubule mechanics. Here, we found that tubulin acetylation is required for the mechanical stabilization of long-lived microtubules in cells. Depletion of the tubulin acetyltransferase TAT1 led to a significant increase in the frequency of microtubule breakage. Nocodazole-resistant microtubules lost upon removal of acetylation were largely restored by either pharmacological or physical removal of compressive forces...
April 21, 2017: Science
https://www.readbyqxmd.com/read/28428405/acetylation-keeps-microtubules-strong
#20
EDITORIAL
Stella M Hurtley
No abstract text is available yet for this article.
April 21, 2017: Science
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