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kinesine motor protein

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https://www.readbyqxmd.com/read/29129530/glutamylation-regulates-transport-specializes-function-and-sculpts-the-structure-of-cilia
#1
Robert O'Hagan, Malan Silva, Ken C Q Nguyen, Winnie Zhang, Sebastian Bellotti, Yasmin H Ramadan, David H Hall, Maureen M Barr
Ciliary microtubules (MTs) are extensively decorated with post-translational modifications (PTMs), such as glutamylation of tubulin tails. PTMs and tubulin isotype diversity act as a "tubulin code" that regulates cytoskeletal stability and the activity of MT-associated proteins such as kinesins. We previously showed that, in C. elegans cilia, the deglutamylase CCPP-1 affects ciliary ultrastructure, localization of the TRP channel PKD-2 and the kinesin-3 KLP-6, and velocity of the kinesin-2 OSM-3/KIF17, whereas a cell-specific α-tubulin isotype regulates ciliary ultrastructure, intraflagellar transport, and ciliary functions of extracellular vesicle (EV)-releasing neurons...
November 2, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29123223/structural-basis-of-small-molecule-atpase-inhibition-of-a-human-mitotic-kinesin-motor-protein
#2
Hee-Won Park, Zhujun Ma, Haizhong Zhu, Shimin Jiang, Robert C Robinson, Sharyn A Endow
Kinesin microtubule motor proteins play essential roles in division, including attaching chromosomes to spindles and crosslinking microtubules for spindle assembly. Human kinesin-14 KIFC1 is unique in that cancer cells with amplified centrosomes are dependent on the motor for viable division because of its ability to cluster centrosomes and form bipolar spindles, but it is not required for division in almost all normal cells. Screens for small molecule inhibitors of KIFC1 have yielded several candidates for further development, but obtaining structural data to determine their sites of binding has been difficult...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29117569/ros-control-mitochondrial-motility-through-p38-and-the-motor-adaptor-miro-trak
#3
Valentina Debattisti, Akos A Gerencser, Masao Saotome, Sudipto Das, György Hajnóczky
Mitochondrial distribution and motility are recognized as central to many cellular functions, but their regulation by signaling mechanisms remains to be elucidated. Here, we report that reactive oxygen species (ROS), either derived from an extracellular source or intracellularly generated, control mitochondrial distribution and function by dose-dependently, specifically, and reversibly decreasing mitochondrial motility in both rat hippocampal primary cultured neurons and cell lines. ROS decrease motility independently of cytoplasmic [Ca(2+)], mitochondrial membrane potential, or permeability transition pore opening, known effectors of oxidative stress...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29115586/characterization-of-kif11-as-a-novel-prognostic-biomarker-and-therapeutic-target-for-oral-cancer
#4
Kayo Daigo, Atsushi Takano, Phung Manh Thang, Yoshihiro Yoshitake, Masanori Shinohara, Iwau Tohnai, Yoshinori Murakami, Jiro Maegawa, Yataro Daigo
Oral cancer has a high mortality rate, and its incidence is increasing gradually worldwide. As the effectiveness of standard treatments is still limited, the development of new therapeutic strategies is eagerly awaited. Kinesin family member 11 (KIF11) is a motor protein required for establishing a bipolar spindle in cell division. The role of KIF11 in oral cancer is unclear. Therefore, the present study aimed to assess the role of KIF11 in oral cancer and evaluate its role as a prognostic biomarker and therapeutic target for treating oral cancer...
October 31, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29111975/kinesin-motility-driven-by-subdomain-dynamics
#5
Wonmuk Hwang, Matthew Lang, Martin Karplus
The microtubule (MT)-associated motor protein kinesin utilizes its conserved ATPase head to achieve diverse motility characteristics. Despite considerable knowledge about how its ATPase activity and MT binding are coupled to the motility cycle, the atomic mechanism of the core events remain to be found. To obtain insights into the mechanism, we performed 38.5 microseconds of all-atom molecular dynamics simulations of kinesin-MT complexes in different nucleotide states. Local subdomain dynamics were found to be essential for nucleotide processing...
November 7, 2017: ELife
https://www.readbyqxmd.com/read/29077851/ciliogenesis-and-cell-cycle-alterations-contribute-to-kif2a-related-malformations-of-cortical-development
#6
Loïc Broix, Laure Asselin, Carla G Silva, Ekaterina L Ivanova, Peggy Tilly, Johan G Gilet, Nicolas Lebrun, Hélène Jagline, Giuseppe Muraca, Yoann Saillour, Nathalie Drouot, Madeline Louise Reilly, Fiona Francis, Alexandre Benmerah, Nadia Bahi-Buisson, Richard Belvindrah, Laurent Nguyen, Juliette D Godin, Jamel Chelly, Maria-Victoria Hinckelmann
Genetic findings reported by our group and others showed that de novo missense variants in the KIF2A gene underlie malformations of brain development called pachygyria and microcephaly. Though KIF2A is known as member of the Kinesin-13 family involved in the regulation of microtubule end dynamics through its ATP dependent MT-depolymerase activity, how KIF2A variants lead to brain malformations is still largely unknown. Using cellular and in utero electroporation approaches, we show here that KIF2A disease-causing variants disrupts projection neuron positioning and interneuron migration, as well as progenitors proliferation...
October 25, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29077261/tau-directs-intracellular-trafficking-by-regulating-the-forces-exerted-by-kinesin-and-dynein-teams
#7
Abdullah R Chaudhary, Florian Berger, Christopher L Berger, Adam G Hendricks
Organelles, proteins, and mRNA are transported bidirectionally along microtubules by plus-end directed kinesin and minus-end directed dynein motors. Microtubules are decorated by microtubule-associated proteins (MAPs) that organize the cytoskeleton, regulate microtubule dynamics and modulate the interaction between motor proteins and microtubules to direct intracellular transport. Tau is a neuronal MAP that stabilizes axonal microtubules and crosslinks them into bundles. Dysregulation of tau leads to a range of neurodegenerative diseases known as tauopathies including Alzheimer's disease (AD)...
October 27, 2017: Traffic
https://www.readbyqxmd.com/read/29073112/dynein-dynactin-is-necessary-for-anterograde-transport-of-mbp-mrna-in-oligodendrocytes-and-for-myelination-in-vivo
#8
Amy L Herbert, Meng-Meng Fu, Catherine M Drerup, Ryan S Gray, Breanne L Harty, Sarah D Ackerman, Thomas O'Reilly-Pol, Stephen L Johnson, Alex V Nechiporuk, Ben A Barres, Kelly R Monk
Oligodendrocytes in the central nervous system produce myelin, a lipid-rich, multilamellar sheath that surrounds axons and promotes the rapid propagation of action potentials. A critical component of myelin is myelin basic protein (MBP), expression of which requires anterograde mRNA transport followed by local translation at the developing myelin sheath. Although the anterograde motor kinesin KIF1B is involved in mbp mRNA transport in zebrafish, it is not entirely clear how mbp transport is regulated. From a forward genetic screen for myelination defects in zebrafish, we identified a mutation in actr10, which encodes the Arp11 subunit of dynactin, a critical activator of the retrograde motor dynein...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29064326/ligand-and-structure-based-in-silico-studies-to-identify-kinesin-spindle-protein-ksp-inhibitors-as-potential-anticancer-agents
#9
Chandrasekaran Balakumar, Muthusamy Ramesh, Chuin Lean Tham, Samukelisiwe Pretty Khathi, Frank Kozielski, Cherukupalli Srinivasulu, Girish A Hampannavar, Nisar Sayyad, Mahmoud E Soliman, Rajshekhar Karpoormath
Kinesin spindle protein (KSP) belongs to the kinesin superfamily of microtubule-based motor proteins. KSPis responsible for the establishment of the bipolar mitotic spindle which mediates cell division. Inhibition of KSP expedites the blockade of the normal cell cycle during mitosis throughthe generation of monoastralMTarrays that finally cause apoptotic cell death. As KSP is highly expressed in proliferating/cancer cells, it has gained considerable attention as a potential drug target for cancer chemotherapy...
October 24, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29061883/kif13a-mediates-influenza-a-virus-ribonucleoproteins-trafficking
#10
Ana Ramos-Nascimento, Bárbara Kellen, Filipe Ferreira, Marta Alenquer, Silvia Vale-Costa, Graça Raposo, Cédric Delevoye, Maria João Amorim
Influenza A is a rapid evolving virus, successful in provoking periodic epidemics and occasional pandemics in humans. Viral assembly is complex as the virus incorporates an eight-partite segmented genome of RNA (in the form of viral ribonucleoproteins, vRNPs). Genome assembly, with implications to public health, is not completely understood. It was reported that vRNPs are transported to the cell surface on Rab11 vesicles using microtubules, but no molecular motor has been assigned to the process. Here, we have identified KIF13A, a member of the kinesin-3 family, as the first molecular motor efficiently transporting vRNP-Rab11 vesicles during IAV infection...
October 23, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29061732/sld5-ensures-centrosomal-resistance-to-congression-forces-by-preserving-centriolar-satellites
#11
Manpreet Kaur, Raksha Devi, Tanushree Ghosh, Md Muntaz Khan, Praveen Kumar, Priyanka, Ananya Kar, Aparna Sharma, Akhil Varshney, Vipin Kumar, Sandeep Saxena
The migration of chromosomes during mitosis is mediated primarily by kinesins that bind to the chromosomes and move along the microtubules, exerting pulling and pushing forces on the centrosomes. We report that a DNA replication protein, Sld5, localizes to the centrosomes resisting the microtubular pulling forces experienced during chromosome congression. In the absence of Sld5, centriolar satellites, which normally cluster around the centrosomes, are dissipated throughout the cytoplasm, resulting in the loss of their known function of recruiting the centrosomal protein, pericentrin...
October 23, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29060936/overexpression-of-kinesin-superfamily-motor-proteins-in-alzheimer-s-disease
#12
Kelly Hares, James Scott Miners, Amelia Jane Cook, Claire Rice, Neil Scolding, Seth Love, Alastair Wilkins
Defects in motor protein-mediated neuronal transport mechanisms have been implicated in a number of neurodegenerative disorders but remain relatively little studied in Alzheimer's disease (AD). Our aim in the present study was to assess the expression of the anterograde kinesin superfamily motor proteins KIF5A, KIF1B, and KIF21B, and to examine their relationship to levels of hyperphosphorylated tau, amyloid-β protein precursor (AβPP), and amyloid-β (Aβ) in human brain tissue. We used a combination of qPCR, immunoblotting, and ELISA to perform these analyses in midfrontal cortex from 49 AD and 46 control brains...
October 16, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29046869/staphylococcus-aureus-alpha-toxin-induces-the-formation-of-dynamic-tubules-labeled-with-lc3-within-host-cells-in-a-rab7-and-rab1b-dependent-manner
#13
María M López de Armentia, María C Gauron, María I Colombo
Staphylococcus aureus is a pathogen that causes severe infectious diseases that eventually lead to septic and toxic shock. S. aureus infection is characterized by the production of virulence factors, including enzymes and toxins. After internalization S. aureus resides in a phagosome labeled with Rab7 protein. Here, we show that S. aureus generates tubular structures marked with the small GTPases Rab1b and Rab7 and by the autophagic protein LC3 at early times post-infection. As shown by live cell imaging these tubular structures are highly dynamic, extend, branch and grow in length...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29045730/ribosomal-protein-ntrpl17-interacts-with-kinesin-12-family-protein-ntkrp-and-functions-in-the-regulation-of-embryo-seed-size-and-radicle-growth
#14
Shujuan Tian, Jingjing Wu, Yuan Liu, Xiaorong Huang, Fen Li, Zhaodan Wang, Meng-Xiang Sun, Miriam Gifford
We previously reported that a novel motor protein belonging to the kinesin-12 family, NtKRP, displays critical roles in regulating embryo and seed size establishment. However, it remains unknown exactly how NtKRP contributes to this developmental process. Here, we report that a 60S ribosomal protein NtRPL17 directly interacts with NtKRP. The phenotypes of NtRPL17 RNAi lines show notable embryo and seed size reduction. Structural observations of the NtRPL17-silenced embryos/seeds reveal that the embryo size reduction is due to a decrease in cell number...
October 14, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29042452/export-of-membrane-proteins-from-the-golgi-complex-to-the-primary-cilium-requires-the-kinesin-motor-kifc1
#15
Si-Hyung Lee, Kwangsic Joo, Eun Ji Jung, Hyowon Hong, Jimyung Seo, Joon Kim
Microtubule-based motors contribute to the efficiency and selectivity of Golgi exit and post-Golgi transport of membrane proteins that are targeted to distinct compartments. Cytoplasmic dynein moves post-Golgi vesicles that carry rhodopsin toward the base of the connecting cilium in photoreceptor cells; however, the identity of the motors that are involved in the vesicular trafficking of ciliary membrane proteins in nonphotoreceptor cells remains unclear. Here, we demonstrate that the minus end-directed kinesin KIFC1 (kinesin family member C1) is required for both ciliary membrane protein transport and serum starvation-induced ciliogenesis in retinal pigmented epithelial 1 cells...
October 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29035362/changes-in-microtubule-overlap-length-regulate-kinesin-14-driven-microtubule-sliding
#16
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/29033361/binding-of-pld2-generated-phosphatidic-acid-to-kif5b-promotes-mt1-mmp-surface-trafficking-and-lung-metastasis-of-mouse-breast-cancer-cells
#17
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 23, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28991265/a-structural-model-for-microtubule-minus-end-recognition-and-protection-by-camsap-proteins
#18
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...
November 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28978447/acetylated-microtubules-are-preferentially-bundled-leading-to-enhanced-kinesin-1-motility
#19
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
#20
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
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