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kinesine motor protein

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https://www.readbyqxmd.com/read/29790963/the-presenilin-loop-region-is-essential-for-glycogen-synthase-kinase-3-beta-mediated-functions-on-motor-proteins-during-axonal-transport
#1
Rupkatha Banerjee, Zoe Rudloff, Crystal Naylor, Michael Yu, Shermali Gunawardena
Neurons require intracellular transport of essential components for function and viability, and defects in transport has been implicated in many neurodegenerative diseases including Alzheimer's disease (AD). One possible mechanism by which transport defects could occur is by improper regulation of molecular motors. Previous work showed that reduction of Presenilin (PS) or Glycogen synthase kinase 3 beta (GSK3β) stimulated APP vesicle motility. Excess GSK3β caused transport defects and increased motor binding to membranes, while reduction of PS decreased active GSK3β and motor binding to membranes...
May 22, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29782552/role-of-kinesins-in-directed-adenovirus-transport-and-cytoplasmic-exploration
#2
Jie Zhou, Julian Scherer, Julie Yi, Richard B Vallee
Many viruses, including adenovirus, exhibit bidirectional transport along microtubules following cell entry. Cytoplasmic dynein is responsible for microtubule minus end transport of adenovirus capsids after endosomal escape. However, the identity and roles of the opposing plus end-directed motor(s) remain unknown. We performed an RNAi screen of 38 kinesins, which implicated Kif5B (kinesin-1 family) and additional minor kinesins in adenovirus 5 (Ad5) capsid translocation. Kif5B RNAi markedly increased centrosome accumulation of incoming Ad5 capsids in human A549 pulmonary epithelial cells within the first 30 min post infection, an effect dramatically enhanced by blocking Ad5 nuclear pore targeting using leptomycin B...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29781531/down-regulation-of-kif2a-inhibits-gastric-cancer-cell-invasion-via-suppressing-mt1-mmp
#3
Peng Zhao, Fei Lan, Hui Zhang, Guangwei Zeng, Dong Liu
Gastric cancer accounts for a sizeable proportion of global cancer mortality with high morbidity and poor prognosis. Kinesin superfamily proteins (KIFs) are microtubule-dependent motor proteins that function as oncogenes in cancer cells, it has been discovered in recent years. Kinesin family member 2a (KIF2A), a member of KIFs, has received attention for its role in carcinogenesis and its prognostic value in several human cancers such as breast cancer, colorectal cancer, and squamous cell carcinoma. However, the role of KIF2A in human gastric cancer remains unknown...
May 21, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29773651/usp25m-protease-regulates-ubiquitin-like-processing-of-tug-proteins-to-control-glut4-glucose-transporter-translocation-in-adipocytes
#4
Estifanos N Habtemichael, Don T Li, Abel Alcázar-Román, Xavier O Westergaard, Muyi Li, Max C Petersen, Hanbing Li, Stephen G DeVries, Eric Li, Omar Julca-Zevallos, Joseph S Wolenski, Jonathan S Bogan
Insulin stimulates the exocytic translocation of specialized vesicles in adipocytes, which inserts GLUT4 glucose transporters into the plasma membrane to enhance glucose uptake.  Previous results support a model in which TUG proteins trap these GLUT4 storage vesicles at the Golgi matrix, and in which insulin triggers endoproteolytic cleavage of TUG to translocate GLUT4.  Here, we identify Usp25m as a protease required for insulin-stimulated TUG cleavage and GLUT4 translocation in adipocytes.  Usp25m is expressed in adipocytes, binds TUG and GLUT4, dissociates from TUG-bound vesicles after insulin addition, and colocalizes with TUG and insulin-responsive cargoes in unstimulated cells...
May 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29771342/recent-progress-in-structural-biology-lessons-from-our-research-history
#5
Ryo Nitta, Tsuyoshi Imasaki, Eriko Nitta
The recent 'resolution revolution' in structural analyses of cryo-electron microscopy (cryo-EM) has drastically changed the research strategy for structural biology. In addition to X-ray crystallography and nuclear magnetic resonance spectroscopy, cryo-EM has achieved the structural analysis of biological molecules at near-atomic resolution, resulting in the Nobel Prize in Chemistry 2017. The effect of this revolution has spread within the biology and medical science fields affecting everything from basic research to pharmaceutical development by visualizing atomic structure...
May 16, 2018: Microscopy
https://www.readbyqxmd.com/read/29762713/snap23-kif5-complex-controls-mglu1-receptor-trafficking
#6
Fabrice Raynaud, Vincent Homburger, Martial Seveno, Oana Vigy, Enora Moutin, Laurent Fagni, Julie Perroy
Metabotropic glutamate receptors are expressed at excitatory synapses and control synaptic transmission in mammalian brain. These receptors are involved in numerous patho-physiological functions. However, little is known about the molecular determinants responsible for their intracellular transport and membrane targeting. Here we investigated the nature of the molecular motor and adaptor protein responsible for trafficking and membrane localization of the group I metabotropic glutamate mGlu1 post-synaptic receptor in cultured hippocampal neurons...
May 14, 2018: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29727692/c11orf70-mutations-disrupting-the-intraflagellar-transport-dependent-assembly-of-multiple-axonemal-dyneins-cause-primary-ciliary-dyskinesia
#7
Mahmoud R Fassad, Amelia Shoemark, Pierrick le Borgne, France Koll, Mitali Patel, Mellisa Dixon, Jane Hayward, Charlotte Richardson, Emily Frost, Lucy Jenkins, Thomas Cullup, Eddie M K Chung, Michel Lemullois, Anne Aubusson-Fleury, Claire Hogg, David R Mitchell, Anne-Marie Tassin, Hannah M Mitchison
Primary ciliary dyskinesia (PCD) is a genetically and phenotypically heterogeneous disorder characterized by destructive respiratory disease and laterality abnormalities due to randomized left-right body asymmetry. PCD is mostly caused by mutations affecting the core axoneme structure of motile cilia that is essential for movement. Genes that cause PCD when mutated include a group that encode proteins essential for the assembly of the ciliary dynein motors and the active transport process that delivers them from their cytoplasmic assembly site into the axoneme...
May 3, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29717133/kinesin-light-chain-4-depletion-induces-apoptosis-of-radioresistant-cancer-cells-by-mitochondrial-dysfunction-via-calcium-ion-influx
#8
Jeong-Hwa Baek, Janet Lee, Hong Shik Yun, Chang-Woo Lee, Jie-Young Song, Hong-Duck Um, Jong Kuk Park, In-Chul Park, Jae-Sung Kim, Eun Ho Kim, Sang-Gu Hwang
Kinesins act as molecular microtubule-dependent motor proteins and have various important cellular functions related to cell division, intracellular transport, and membrane trafficking. However, the function of kinesin light chain 4 (KLC4) in cancer, especially radioresistance, has not been previously described. Thus, we investigated KLC4 function in lung cancer cells and radioresistant R-H460 cells by analyzing alterations in radiosensitivity after gene knockdown with siRNA and by evaluating cellular phenotypes and xenograft tumor growth...
May 2, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29716949/motor-proteins
#9
REVIEW
H Lee Sweeney, Erika L F Holzbaur
SUMMARYMyosin motors power movements on actin filaments, whereas dynein and kinesin motors power movements on microtubules. The mechanisms of these motor proteins differ, but, in all cases, ATP hydrolysis and subsequent release of the hydrolysis products drives a cycle of interactions with the track (either an actin filament or a microtubule), resulting in force generation and directed movement.
May 1, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/29706510/coin-tossing-explains-the-activity-of-opposing-microtubule-motors-on-phagosomes
#10
Paulomi Sanghavi, Ashwin D'Souza, Ashim Rai, Arpan Rai, Ranjith Padinhatheeri, Roop Mallik
How the opposing activity of kinesin and dynein motors generates polarized distribution of organelles inside cells is poorly understood and hotly debated [1, 2]. Possible explanations include stochastic mechanical competition [3, 4], coordinated regulation by motor-associated proteins [5-7], mechanical activation of motors [8], and lipid-induced organization [9]. Here, we address this question by using phagocytosed latex beads to generate early phagosomes (EPs) that move bidirectionally along microtubules (MTs) in an in vitro assay [9]...
April 13, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29695795/cryo-em-reveals-the-structural-basis-of-microtubule-depolymerization-by-kinesin-13s
#11
Matthieu P M H Benoit, Ana B Asenjo, Hernando Sosa
Kinesin-13s constitute a distinct group within the kinesin superfamily of motor proteins that promote microtubule depolymerization and lack motile activity. The molecular mechanism by which kinesin-13s depolymerize microtubules and are adapted to perform a seemingly very different activity from other kinesins is still unclear. To address this issue, here we report the near atomic resolution cryo-electron microscopy (cryo-EM) structures of Drosophila melanogaster kinesin-13 KLP10A protein constructs bound to curved or straight tubulin in different nucleotide states...
April 25, 2018: Nature Communications
https://www.readbyqxmd.com/read/29694156/limited-resources-induce-bistability-in-microtubule-length-regulation
#12
Matthias Rank, Aniruddha Mitra, Louis Reese, Stefan Diez, Erwin Frey
The availability of protein is an important factor for the determination of the size of the mitotic spindle. Involved in spindle-size regulation is kinesin-8, a molecular motor and microtubule (MT) depolymerase, which is known to tightly control MT length. Here, we propose and analyze a theoretical model in which kinesin-induced MT depolymerization competes with spontaneous polymerization while supplies of both tubulin and kinesin are limited. In contrast to previous studies where resources were unconstrained, we find that, for a wide range of concentrations, MT length regulation is bistable...
April 6, 2018: Physical Review Letters
https://www.readbyqxmd.com/read/29688812/nitration-of-microtubules-blocks-axonal-mitochondrial-transport-in-a-human-pluripotent-stem-cell-model-of-parkinson-s-disease
#13
Morgan G Stykel, Kayla Humphries, Mathew P Kirby, Chris Czaniecki, Tinya Wang, Tammy Ryan, Vladimir Bamm, Scott D Ryan
Neuronal loss in Parkinson's disease (PD) is associated with aberrant mitochondrial function in dopaminergic (DA) neurons of the substantia nigra pars compacta. An association has been reported between PD onset and exposure to mitochondrial toxins, including the agrochemicals paraquat (PQ), maneb (MB), and rotenone (Rot). Here, with the use of a patient-derived stem cell model of PD, allowing comparison of DA neurons harboring a mutation in the α-synuclein (α-syn) gene ( SNCA-A53T) against isogenic, mutation-corrected controls, we describe a novel mechanism whereby NO, generated from SNCA-A53T mutant neurons exposed to Rot or PQ/MB, inhibits anterograde mitochondrial transport through nitration of α-tubulin (α-Tub)...
April 24, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29684553/fission-yeast-cells-overproducing-hset-kifc1-provides-a-useful-tool-for-identification-and-evaluation-of-human-kinesin-14-inhibitors
#14
Masashi Yukawa, Tomoaki Yamauchi, Naoaki Kurisawa, Shakil Ahmed, Ken-Ichi Kimura, Takashi Toda
Many human cancer cells contain more than two centrosomes, yet these cancer cells can form pseudo-bipolar spindles through the mechanism, called centrosome clustering, and survive, instead of committing lethal multipolar mitoses. Kinesin-14/HSET, a minus end-directed motor, plays a crucial role in centrosome clustering. Accordingly, HSET is deemed to be a promising chemotherapeutic target to selectively kill cancer cells. Recently, three HSET inhibitors (AZ82, CW069 and SR31527) have been reported, but their specificity and efficacy have not been evaluated rigorously...
April 20, 2018: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/29670958/large-scale-chirality-in-an-active-layer-of-microtubules-and-kinesin-motor-proteins
#15
Kyongwan Kim, Natsuhiko Yoshinaga, Sanjib Bhattacharyya, Hikaru Nakazawa, Mitsuo Umetsu, Winfried Teizer
During the early developmental process of organisms, the formation of left-right laterality requires a subtle mechanism, as it is associated with other principal body axes. Any inherent chiral feature in an egg cell can in principal trigger this spontaneous breaking of chiral symmetry. Individual microtubules, major cytoskeletal filaments, are known as chiral objects. However, to date there lacks convincing evidence of a hierarchical connection of the molecular nature of microtubules to large-scale chirality, particularly at the length scale of an entire cell...
April 19, 2018: Soft Matter
https://www.readbyqxmd.com/read/29662074/competition-between-microtubule-associated-proteins-directs-motor-transport
#16
Brigette Y Monroy, Danielle L Sawyer, Bryce E Ackermann, Melissa M Borden, Tracy C Tan, Kassandra M Ori-McKenney
Within cells, motor and non-motor microtubule-associated proteins (MAPs) simultaneously converge on the microtubule. How the binding activities of non-motor MAPs are coordinated and how they contribute to the balance and distribution of motor transport is unknown. Here, we examine the relationship between MAP7 and tau owing to their antagonistic roles in vivo. We find that MAP7 and tau compete for binding to microtubules, and determine a mechanism by which MAP7 displaces tau from the lattice. MAP7 promotes kinesin-based transport in vivo and strongly recruits kinesin-1 to the microtubule in vitro, providing evidence for direct enhancement of motor motility by a MAP...
April 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29656322/p190rhogap-prevents-mitotic-spindle-fragmentation-and-is-required-to-activate-aurora-a-kinase-at-acentriolar-poles
#17
Arkadi Manukyan, Lilit Sargsyan, Sarah J Parsons, P Todd Stukenberg
Assembly of the mitotic spindle is essential for proper chromosome segregation during mitosis. Maintenance of spindle poles requires precise regulation of kinesin- and dynein-generated forces, and improper regulation of these forces disrupts pole integrity leading to pole fragmentation. The formation and function of the mitotic spindle are regulated by many proteins, including Aurora A kinase and the motor proteins Kif2a and Eg5. Here, we characterize a surprising role for the RhoA GTPase-activating protein, p190RhoGAP, in regulating the mitotic spindle...
April 14, 2018: Chromosoma
https://www.readbyqxmd.com/read/29620256/kifc1-a-novel-potential-prognostic-factor-and-therapeutic-target-in-hepatocellular-carcinoma
#18
Xiaowei Fu, Yaqiong Zhu, Bingbing Zheng, Yeqing Zou, Chao Wang, Peng Wu, Jun Wang, Haimin Chen, Pengcheng Du, Bo Liang, Lu Fang
Kinesin family member C1 (KIFC1, also known as HSET) is a minus end-directed motor protein, which is critical in centrosome clustering. The present study investigated the expression of KIFC1 in paired hepatocellular carcinoma (HCC) tissues and adjacent non-cancerous tissues from 91 patients by immunohistochemical analysis; clinical data were concomitantly collected. KIFC1 was expressed at high levels in HCC tissues, compared with that in peritumoral tissues (54.9 vs. 14.3%; P<0.01), and its expression correlated with tumor emboli, metastasis, recurrence and time of recurrence...
March 29, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29606421/a-camp-pka-kinesin-1-axis-promotes-the-axonal-transport-of-mitochondria-in-aging-drosophila-neurons
#19
Alessio Vagnoni, Simon L Bullock
Mitochondria play fundamental roles within cells, including energy provision, calcium homeostasis, and the regulation of apoptosis. The transport of mitochondria by microtubule-based motors is critical for neuronal structure and function. This process allows local requirements for mitochondrial functions to be met and also facilitates recycling of these organelles [1, 2]. An age-related reduction in mitochondrial transport has been observed in neurons of mammalian and non-mammalian organisms [3-6], and has been proposed to contribute to the broader decline in neuronal function that occurs during aging [3, 5-7]...
March 20, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29604873/a-fluid-membrane-enhances-the-velocity-of-cargo-transport-by-small-teams-of-kinesin-1
#20
Qiaochu Li, Kuo-Fu Tseng, Stephen J King, Weihong Qiu, Jing Xu
Kinesin-1 (hereafter referred to as kinesin) is a major microtubule-based motor protein for plus-end-directed intracellular transport in live cells. While the single-molecule functions of kinesin are well characterized, the physiologically relevant transport of membranous cargos by small teams of kinesins remains poorly understood. A key experimental challenge remains in the quantitative control of the number of motors driving transport. Here we utilized "motile fraction" to overcome this challenge and experimentally accessed transport by a single kinesin through the physiologically relevant transport by a small team of kinesins...
March 28, 2018: Journal of Chemical Physics
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