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https://www.readbyqxmd.com/read/29036226/structural-plasticity-of-the-n-terminal-capping-helix-of-the-tpr-domain-of-kinesin-light-chain
#1
The Quyen Nguyen, Mélanie Chenon, Fernando Vilela, Christophe Velours, Magali Aumont-Nicaise, Jessica Andreani, Paloma F Varela, Paola Llinas, Julie Ménétrey
Kinesin1 plays a major role in neuronal transport by recruiting many different cargos through its kinesin light chain (KLC). Various structurally unrelated cargos interact with the conserved tetratricopeptide repeat (TPR) domain of KLC. The N-terminal capping helix of the TPR domain exhibits an atypical sequence and structural features that may contribute to the versatility of the TPR domain to bind different cargos. We determined crystal structures of the TPR domain of both KLC1 and KLC2 encompassing the N-terminal capping helix and show that this helix exhibits two distinct and defined orientations relative to the rest of the TPR domain...
2017: PloS One
https://www.readbyqxmd.com/read/29035362/changes-in-microtubule-overlap-length-regulate-kinesin-14-driven-microtubule-sliding
#2
Marcus Braun, Zdenek Lansky, Agata Szuba, Friedrich W Schwarz, Aniruddha Mitra, Mengfei Gao, Annemarie Lüdecke, Pieter Rein Ten Wolde, Stefan Diez
Microtubule-crosslinking motor proteins, which slide antiparallel microtubules, are required for the remodeling of microtubule networks. Hitherto, all microtubule-crosslinking motors have been shown to slide microtubules at a constant velocity until no overlap remains between them, leading to the breakdown of the initial microtubule geometry. Here, we show in vitro that the sliding velocity of microtubules, driven by human kinesin-14 HSET, decreases when microtubules start to slide apart, resulting in the maintenance of finite-length microtubule overlaps...
October 16, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/29035202/localised-dynactin-protects-growing-microtubules-to-deliver-oskar-mrna-to-the-posterior-cortex-of-the-drosophila-oocyte
#3
Ross Nieuwburg, Dmitry Nashchekin, Maximilian Jakobs, Andrew P Carter, Philipp Khuc Trong, Raymond E Goldstein, Daniel St Johnston
The localisation of oskar mRNA to the posterior of the Drosophila oocyte defines where the abdomen and germ cells form in the embryo. Kinesin 1 transports oskar mRNA to the oocyte posterior along a polarised microtubule cytoskeleton that grows from non-centrosomal microtubule organising centres (ncMTOCs) along the anterior/lateral cortex. Here, we show that the formation of this polarised microtubule network also requires the posterior regulation of microtubule growth. A missense mutation in the dynactin Arp1 subunit causes most oskar mRNA to localise in the posterior cytoplasm rather than cortically...
October 16, 2017: ELife
https://www.readbyqxmd.com/read/29033361/binding-of-pld2-generated-phosphatidic-acid-to-kif5b-promotes-mt1-mmp-surface-trafficking-and-lung-metastasis-of-mouse-breast-cancer-cells
#4
Ziqing Wang, Feng Zhang, Jingquan He, Ping Wu, Li Wei Rachel Tay, Ming Cai, Weiqi Nian, Yuanyuan Weng, Li Qin, Jeffrey T Chang, Laura B McIntire, Gilbert Di Paolo, Jianming Xu, Junmin Peng, Guangwei Du
Little is known about the cellular events promoting metastasis. We show that knockout of phospholipase D2 (PLD2), which generates the signaling lipid phosphatidic acid (PA), inhibits lung metastases in the mammary tumor virus (MMTV)-Neu transgenic mouse breast cancer model. PLD2 promotes local invasion through the regulation of the plasma membrane targeting of MT1-MMP and its associated invadopodia. A liposome pull-down screen identifies KIF5B, the heavy chain of the motor protein kinesin-1, as a new PA-binding protein...
October 11, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29023785/cns-synapses-are-stabilized-trans-synaptically-by-laminins-and-laminin-interacting-proteins
#5
Dale D Hunter, Mary K Manglapus, Galina Bachay, Thomas Claudepierre, Michael W Dolan, Kelly-Ann Gesuelli, William J Brunken
The retina expresses several laminins in the outer plexiform layer (OPL), where they may provide an extracellular scaffold for synapse stabilization. Mice with a targeted deletion of the laminin β2 gene (Lamb2) exhibit retinal disruptions: photoreceptor synapses in the OPL are disorganized and the retinal physiological response is attenuated. We hypothesize that laminins are required for proper trans-synaptic alignment. To test this, we compared the distribution, expression, association and modification of several pre- and post-synaptic elements in wild-type and Lamb2-null retinae...
October 12, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/29023446/towards-elimination-of-visceral-leishmaniasis-in-the-indian-subcontinent-translating-research-to-practice-to-public-health
#6
REVIEW
Siddhivinayak Hirve, Axel Kroeger, Greg Matlashewski, Dinesh Mondal, Megha Raj Banjara, Pradeep Das, Ahmed Be-Nazir, Byron Arana, Piero Olliaro
BACKGROUND: The decade following the Regional Strategic Framework for Visceral Leishmaniasis (VL) elimination in 2005 has shown compelling progress in the reduction of VL burden in the Indian subcontinent. The Special Programme for Research and Training in Tropical Diseases (TDR), hosted by the World Health Organization (WHO) and other stakeholders, has coordinated and financed research for the development of new innovative tools and strategies to support the regional VL elimination initiative...
October 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29021344/a-microtubule-polymerase-cooperates-with-the-kinesin-6-motor-and-a-microtubule-crosslinker-to-promote-bipolar-spindle-assembly-in-the-absence-of-kinesin-5-and-kinesin-14-in-fission-yeast
#7
Masashi Yukawa, Tomoki Kawakami, Masaki Okazaki, Kazunori Kume, Ngang Heok Tang, Takashi Toda
Accurate chromosome segregation relies on the bipolar mitotic spindle. In many eukaryotes, spindle formation is driven by the plus-end directed motor Kinesin-5 that generates outward force to establish spindle bipolarity. Its inhibition leads to the emergence of monopolar spindles with mitotic arrest. Intriguingly, simultaneous inactivation of the minus-end directed motor Kinesin-14 restores spindle bipolarity in many systems. Here we show that in fission yeast, three independent pathways contribute to spindle bipolarity in the absence of Kinesin-5/Cut7 and Kinesin-14/Pkl1...
October 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28993508/personalized-sirna-nanoparticle-systemic-therapy-using-metastatic-lymph-node-specimens-obtained-with-ebus-tbna-in-lung-cancer
#8
Tatsuya Kato, Daiyoon Lee, Huang Huang, William Cruz-Munoz, Hideki Ujiie, Kosuke Fujino, Hironobu Wada, Priya Patel, Hsin-Pei Hu, Kentaro Hirohashi, Takahiro Nakajima, Masaaki Sato, Mitsuhito Kaji, Kichizo Kaga, Yoshiro Matsui, Juan Chen, Gang Zheng, Kazuhiro Yasufuku
Inhibiting specific gene expression with short interfering RNA (siRNA) provides a new therapeutic strategy to tackle many diseases at the molecular level. Recent strategies called high-density lipoprotein (HDL)-mimicking peptide-phospholipid nanoscaffold (HPPS) nanoparticles have been used to induce siRNAs-targeted delivery to scavenger receptor class B type I receptor (SCARB1) expressing cancer cells with high efficiency. Here, eight ideal therapeutic target genes were identified for advanced lung cancer throughout the screenings using endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA) and the establishment of a personalized siRNA-nanoparticle therapy...
October 9, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28993468/a-ragulator-borc-interaction-controls-lysosome-positioning-in-response-to-amino-acid-availability
#9
Jing Pu, Tal Keren-Kaplan, Juan S Bonifacino
Lysosomes play key roles in the cellular response to amino acid availability. Depletion of amino acids from the medium turns off a signaling pathway involving the Ragulator complex and the Rag guanosine triphosphatases (GTPases), causing release of the inactive mammalian target of rapamycin complex 1 (mTORC1) serine/threonine kinase from the lysosomal membrane. Decreased phosphorylation of mTORC1 substrates inhibits protein synthesis while activating autophagy. Amino acid depletion also causes clustering of lysosomes in the juxtanuclear area of the cell, but the mechanisms responsible for this phenomenon are poorly understood...
October 9, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28991265/a-structural-model-for-microtubule-minus-end-recognition-and-protection-by-camsap-proteins
#10
Joseph Atherton, Kai Jiang, Marcel M Stangier, Yanzhang Luo, Shasha Hua, Klaartje Houben, Jolien J E van Hooff, Agnel-Praveen Joseph, Guido Scarabelli, Barry J Grant, Anthony J Roberts, Maya Topf, Michel O Steinmetz, Marc Baldus, Carolyn A Moores, Anna Akhmanova
CAMSAP and Patronin family members regulate microtubule minus-end stability and localization and thus organize noncentrosomal microtubule networks, which are essential for cell division, polarization and differentiation. Here, we found that the CAMSAP C-terminal CKK domain is widely present among eukaryotes and autonomously recognizes microtubule minus ends. Through a combination of structural approaches, we uncovered how mammalian CKK binds between two tubulin dimers at the interprotofilament interface on the outer microtubule surface...
October 9, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28986254/enhanced-stability-of-kinesin-1-as-a-function-of-temperature
#11
K Chase, F Doval, M Vershinin
Kinesin-1 is a mechanochemical enzyme which mediates long distance intracellular cargo transport along microtubules in a wide variety of eukaryotic cells. Kinesin is also relatively easy to purify and shows robust function in vitro, leading to numerous proposals for using the kinesin-1/microtubule system for nanoscale transport in engineered devices. However, kinesin in vitro shows signs of degradation at ∼30 °C which severely limits its usability in biomimetic engineering. Notably, kinesin-1 functions robustly in animal cells at body temperatures as high as 40 °C which suggests that kinesin functioning can be stabilized beyond what is observed in vitro...
October 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28980869/regulation-of-autophagic-lysosome-reformation-by-kinesin-1-clathrin-and-phosphatidylinositol-4-5-bisphosphate
#12
Xu Liu, Daniel J Klionsky
No abstract text is available yet for this article.
October 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28978447/acetylated-microtubules-are-preferentially-bundled-leading-to-enhanced-kinesin-1-motility
#13
Linda Balabanian, Christopher L Berger, Adam G Hendricks
The motor proteins kinesin and dynein transport organelles, mRNA, proteins, and signaling molecules along the microtubule cytoskeleton. In addition to serving as tracks for transport, the microtubule cytoskeleton directs intracellular trafficking by regulating the activity of motor proteins through the organization of the filament network, microtubule-associated proteins, and tubulin posttranslational modifications. However, it is not well understood how these factors influence motor motility, and in vitro assays and live cell observations often produce disparate results...
October 3, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28977938/high-eg5-expression-predicts-poor-prognosis-in-breast-cancer
#14
Qin Jin, Fang Huang, Xudong Wang, Huijun Zhu, Yun Xian, Jieying Li, Shu Zhang, Qichao Ni
Eg5 is a motor protein belonging to the kinesin-5 family and has been suggested to exert important function in tumors. In this study, we determined the mRNA and protein expression levels of Eg5 in cancerous and non-cancerous breast tissue by quantitative real-time polymerase chain reaction (qRT-PCR) and tissue microarray immunohistochemistry analysis (TMA-IHC) respectively. The results of 20 fresh-frozen BC samples demonstrated that Eg5 mRNA levels were significantly higher in BC tissues compared with corresponding non-cancerous tissue (p = 0...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977870/c-terminal-kinesin-motor-kifc1-participates-in-facilitating-proper-cell-division-of-human-seminoma
#15
Yu-Xi Xiao, Hao-Qing Shen, Zhen-Yu She, Li Sheng, Qian-Qian Chen, Yu-Lan Chu, Fu-Qing Tan, Wan-Xi Yang
C-terminus kinesin motor KIFC1 is known for centrosome clustering in cancer cells with supernumerary centrosomes. KIFC1 crosslinks and glides on microtubules (MT) to assist normal bipolar spindle formation to avoid multi-polar cell division, which might be fatal. Testis cancer is the most common human cancer among young men. However, the gene expression profiles of testis cancer is still not complete and the expression of the C-terminus kinesin motor KIFC1 in testis cancer has not yet been examined. We found that KIFC1 is enriched in seminoma tissues in both mRNA level and protein level, and is specifically enriched in the cells that divide actively...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28973906/kinesin-rotates-unidirectionally-and-generates-torque-while-walking-on-microtubules
#16
Avin Ramaiya, Basudev Roy, Michael Bugiel, Erik Schäffer
Cytoskeletal motors drive many essential cellular processes. For example, kinesin-1 transports cargo in a step-wise manner along microtubules. To resolve rotations during stepping, we used optical tweezers combined with an optical microprotractor and torsion balance using highly birefringent microspheres to directly and simultaneously measure the translocation, rotation, force, and torque generated by individual kinesin-1 motors. While, at low adenosine 5'-triphosphate (ATP) concentrations, motors did not generate torque, we found that motors translocating along microtubules at saturating ATP concentrations rotated unidirectionally, producing significant torque on the probes...
September 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28973894/molecular-origin-of-the-weak-susceptibility-of-kinesin-velocity-to-loads-and-its-relation-to-the-collective-behavior-of-kinesins
#17
Qian Wang, Michael R Diehl, Biman Jana, Margaret S Cheung, Anatoly B Kolomeisky, José N Onuchic
Motor proteins are active enzymatic molecules that support important cellular processes by transforming chemical energy into mechanical work. Although the structures and chemomechanical cycles of motor proteins have been extensively investigated, the sensitivity of a motor's velocity in response to a force is not well-understood. For kinesin, velocity is weakly influenced by a small to midrange external force (weak susceptibility) but is steeply reduced by a large force. Here, we utilize a structure-based molecular dynamic simulation to study the molecular origin of the weak susceptibility for a single kinesin...
September 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28973175/amyotrophic-lateral-sclerosis-associated-mutant-sod1-inhibits-anterograde-axonal-transport-of-mitochondria-by-reducing-miro1-levels
#18
Annekathrin Moller, Claudia S Bauer, Rebecca N Cohen, Christopher P Webster, Kurt J De Vos
Defective axonal transport is an early neuropathological feature of amyotrophic lateral sclerosis (ALS). We have previously shown that ALS-associated mutations in Cu/Zn superoxide dismutase 1 (SOD1) impair axonal transport of mitochondria in motor neurons isolated from SOD1 G93A transgenic mice and in ALS mutant SOD1 transfected cortical neurons, but the underlying mechanisms remained unresolved.The outer mitochondrial membrane protein mitochondrial Rho GTPase 1 (Miro1) is a master regulator of mitochondrial axonal transport in response to cytosolic calcium (Ca2+) levels ([Ca2+]c) and mitochondrial damage...
September 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28972769/motility-of-microtubules-on-the-inner-surface-of-water-in-oil-emulsion-droplets
#19
Mikako Tsuji, Arif Md Rashedul Kabir, Masaki Ito, Daisuke Inoue, Kenta Kokado, Kazuki Sada, Akira Kakugo
The water-in-oil emulsion systems have recently been attracting much attention in various fields. However, functionalization of the water-in-oil emulsion systems, which is required for expanding their applications in industry and research, has been challenging. We now demonstrate functionalization of a water-in-oil emulsion system by anchoring a target protein molecule. A microtubule associated motor protein kinesin-1 was successfully anchored to the inner surface of water-in-oil emulsion droplets by employing the specific interaction of the nickel-nitrilotriacetic acid (NTA)-histidine tag...
October 3, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28966089/nesprin-1%C3%AE-dependent-microtubule-nucleation-from-the-nuclear-envelope-via-akap450-is-necessary-for-nuclear-positioning-in-muscle-cells
#20
Petra Gimpel, Yin Loon Lee, Radoslaw M Sobota, Alessandra Calvi, Victoria Koullourou, Rutti Patel, Kamel Mamchaoui, François Nédélec, Sue Shackleton, Jan Schmoranzer, Brian Burke, Bruno Cadot, Edgar R Gomes
The nucleus is the main microtubule-organizing center (MTOC) in muscle cells due to the accumulation of centrosomal proteins and microtubule (MT) nucleation activity at the nuclear envelope (NE) [1-4]. The relocalization of centrosomal proteins, including Pericentrin, Pcm1, and γ-tubulin, depends on Nesprin-1, an outer nuclear membrane (ONM) protein that connects the nucleus to the cytoskeleton via its N-terminal region [5-7]. Nesprins are also involved in the recruitment of kinesin to the NE and play a role in nuclear positioning in skeletal muscle cells [8-12]...
October 9, 2017: Current Biology: CB
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