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kinesine motor protein

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https://www.readbyqxmd.com/read/29351809/axonal-transport-in-a-peripheral-diabetic-neuropathy-model-sex-dimorphic-features
#1
Marzia Pesaresi, Silvia Giatti, Roberto Spezzano, Simone Romano, Silvia Diviccaro, Tiziana Borsello, Nico Mitro, Donatella Caruso, Luis Miguel Garcia-Segura, Roberto Cosimo Melcangi
BACKGROUND: Disruption of axonal transport plays a pivotal role in diabetic neuropathy. A sex-dimorphism exists in the incidence and symptomatology of diabetic neuropathy; however, no studies so far have addressed sex differences in axonal motor proteins expression in early diabetes as well as the possible involvement of neuroactive steroids. Interestingly, recent data point to a role for mitochondria in the sexual dimorphism of neurodegenerative diseases. Mitochondria have a fundamental role in axonal transport by producing the motors' energy source, ATP...
January 19, 2018: Biology of Sex Differences
https://www.readbyqxmd.com/read/29349444/non-invasive-force-measurement-reveals-the-number-of-active-kinesins-on-a-synaptic-vesicle-precursor-in-axonal-transport-regulated-by-arl-8
#2
Kumiko Hayashi, Shin Hasegawa, Takashi Sagawa, Sohei Tasaki, Shinsuke Niwa
Kinesin superfamily protein UNC-104, a member of the kinesin-3 family, transports synaptic vesicle precursors (SVPs). In this study, the number of active UNC-104 molecules hauling a single SVP in axons in the worm Caenorhabditis elegans was counted by applying a newly developed non-invasive force measurement technique. The distribution of the force acting on a SVP transported by UNC-104 was spread out over several clusters, implying the presence of several force-producing units (FPUs). We then compared the number of FPUs in the wild-type worms with that in arl-8 gene-deletion mutant worms...
January 19, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29343805/biallelic-variants-in-kif14-cause-intellectual-disability-with-microcephaly
#3
Periklis Makrythanasis, Reza Maroofian, Asbjørg Stray-Pedersen, Damir Musaev, Maha S Zaki, Iman G Mahmoud, Laila Selim, Amera Elbadawy, Shalini N Jhangiani, Zeynep H Coban Akdemir, Tomasz Gambin, Hanne S Sorte, Arvid Heiberg, Jennifer McEvoy-Venneri, Kiely N James, Valentina Stanley, Denice Belandres, Michel Guipponi, Federico A Santoni, Najmeh Ahangari, Fatemeh Tara, Mohammad Doosti, Justyna Iwaszkiewicz, Vincent Zoete, Paul Hoff Backe, Hanan Hamamy, Joseph G Gleeson, James R Lupski, Ehsan Ghayoor Karimiani, Stylianos E Antonarakis
Kinesin proteins are critical for various cellular functions such as intracellular transport and cell division, and many members of the family have been linked to monogenic disorders and cancer. We report eight individuals with intellectual disability and microcephaly from four unrelated families with parental consanguinity. In the affected individuals of each family, homozygosity for likely pathogenic variants in KIF14 were detected; two loss-of-function (p.Asn83Ilefs*3 and p.Ser1478fs), and two missense substitutions (p...
January 17, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29342275/hot-spot-kif5a-mutations-cause-familial-als
#4
David Brenner, Rüstem Yilmaz, Kathrin Müller, Torsten Grehl, Susanne Petri, Thomas Meyer, Julian Grosskreutz, Patrick Weydt, Wolfgang Ruf, Christoph Neuwirth, Markus Weber, Susana Pinto, Kristl G Claeys, Berthold Schrank, Berit Jordan, Antje Knehr, Kornelia Günther, Annemarie Hübers, Daniel Zeller, Christian Kubisch, Sibylle Jablonka, Michael Sendtner, Thomas Klopstock, Mamede de Carvalho, Anne Sperfeld, Guntram Borck, Alexander E Volk, Johannes Dorst, Joachim Weis, Markus Otto, Joachim Schuster, Kelly Del Tredici, Heiko Braak, Karin M Danzer, Axel Freischmidt, Thomas Meitinger, Tim M Strom, Albert C Ludolph, Peter M Andersen, Jochen H Weishaupt
Heterozygous missense mutations in the N-terminal motor or coiled-coil domains of the kinesin family member 5A (KIF5A) gene cause monogenic spastic paraplegia (HSP10) and Charcot-Marie-Tooth disease type 2 (CMT2). Moreover, heterozygous de novo frame-shift mutations in the C-terminal domain of KIF5A are associated with neonatal intractable myoclonus, a neurodevelopmental syndrome. These findings, together with the observation that many of the disease genes associated with amyotrophic lateral sclerosis disrupt cytoskeletal function and intracellular transport, led us to hypothesize that mutations in KIF5A are also a cause of amyotrophic lateral sclerosis...
January 12, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29337076/opposing-kinesin-and-myosin-i-motors-drive-membrane-deformation-and-tubulation-along-engineered-cytoskeletal-networks
#5
Betsy B McIntosh, Serapion Pyrpassopoulos, Erika L F Holzbaur, E Michael Ostap
Microtubule and actin filament molecular motors such as kinesin-1 and myosin-Ic (Myo1c) transport and remodel membrane-bound vesicles; however, it is unclear how they coordinate to accomplish these tasks. We introduced kinesin-1- and Myo1c-bound giant unilamellar vesicles (GUVs) into a micropatterned in vitro cytoskeletal matrix modeled after the subcellular architecture where vesicular sorting and membrane remodeling are observed. This array was composed of sparse microtubules intersecting regions dense with actin filaments, and revealed that Myo1c-dependent tethering of GUVs enabled kinesin-1-driven membrane deformation and tubulation...
January 9, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29318877/reversibly-bound-kinesin-1-motor-proteins-propelling-microtubules-demonstrate-dynamic-recruitment-of-active-building-blocks
#6
Amy Tsui-Chi Lam, Stanislav Tsitkov, Yifei Zhang, Henry Hess
Biological materials and systems often dynamically self-assemble and disassemble, forming temporary structures as needed and allowing for dynamic responses to stimuli and changing environmental conditions. However, this dynamic interplay of localized component recruitment and release has been difficult to achieve in artificial molecular-scale systems, which are usually designed to have long-lasting, stable bonds. Here, we report the experimental realization of a molecular-scale system that dynamically assembles and disassembles its building blocks while retaining functionality...
January 10, 2018: Nano Letters
https://www.readbyqxmd.com/read/29311115/miro-proteins-coordinate-microtubule-and-actin-dependent-mitochondrial-transport-and-distribution
#7
Guillermo López-Doménech, Christian Covill-Cooke, Davor Ivankovic, Els F Halff, David F Sheehan, Rosalind Norkett, Nicol Birsa, Josef T Kittler
In the current model of mitochondrial trafficking, Miro1 and Miro2 Rho-GTPases regulate mitochondrial transport along microtubules by linking mitochondria to kinesin and dynein motors. By generating Miro1/2 double-knockout mouse embryos and single- and double-knockout embryonic fibroblasts, we demonstrate the essential and non-redundant roles of Miro proteins for embryonic development and subcellular mitochondrial distribution. Unexpectedly, the TRAK1 and TRAK2 motor protein adaptors can still localise to the outer mitochondrial membrane to drive anterograde mitochondrial motility in Miro1/2 double-knockout cells...
January 8, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29296987/generic-maps-of-optimality-reveal-two-chemomechanical-coupling-regimes-for-motor-proteins-from-f1-atpase-and-kinesin-to-myosin-and-cytoplasmic-dynein
#8
Zhisong Wang
Many motor proteins achieve high efficiency for chemomechanical conversion, and single-molecule force-resisting experiments are a major tool to detect the chemomechanical coupling of efficient motors. Here, we introduce several quantitative relations that involve only parameters extracted from force-resisting experiments and offer new benchmarks beyond mere efficiency to judge the chemomechanical optimality or deficit of evolutionary remote motors on the same footing. The relations are verified by the experimental data from F1-ATPase, kinesin-1, myosin V and cytoplasmic dynein, which are representative members of four motor protein families...
January 3, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/29276125/nek9-phosphorylation-defines-a-new-role-for-tpx2-in-eg5-dependent-centrosome-separation-before-nuclear-envelope-breakdown
#9
Susana Eibes, Núria Gallisà-Suñé, Miquel Rosas-Salvans, Paula Martínez-Delgado, Isabelle Vernos, Joan Roig
Centrosomes [1, 2] play a central role during spindle assembly in most animal cells [3]. In early mitosis, they organize two symmetrical microtubule arrays that upon separation define the two poles of the forming spindle. Centrosome separation is tightly regulated [4, 5], occurring through partially redundant mechanisms that rely on the action of microtubule-based dynein and kinesin motors and the actomyosin system [6]. While centrosomes can separate in prophase or in prometaphase after nuclear envelope breakdown (NEBD), prophase centrosome separation optimizes spindle assembly and minimizes the occurrence of abnormal chromosome attachments that could end in aneuploidy [7, 8]...
December 13, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29261664/prion-protein-inhibits-fast-axonal-transport-through-a-mechanism-involving-casein-kinase-2
#10
Emiliano Zamponi, Fiamma Buratti, Gabriel Cataldi, Hector Hugo Caicedo, Yuyu Song, Lisa M Jungbauer, Mary J LaDu, Mariano Bisbal, Alfredo Lorenzo, Jiyan Ma, Pablo R Helguera, Gerardo A Morfini, Scott T Brady, Gustavo F Pigino
Prion diseases include a number of progressive neuropathies involving conformational changes in cellular prion protein (PrPc) that may be fatal sporadic, familial or infectious. Pathological evidence indicated that neurons affected in prion diseases follow a dying-back pattern of degeneration. However, specific cellular processes affected by PrPc that explain such a pattern have not yet been identified. Results from cell biological and pharmacological experiments in isolated squid axoplasm and primary cultured neurons reveal inhibition of fast axonal transport (FAT) as a novel toxic effect elicited by PrPc...
2017: PloS One
https://www.readbyqxmd.com/read/29235081/overview-of-the-mechanism-of-cytoskeletal-motors-based-on-structure
#11
REVIEW
Yusuke Kato, Takuya Miyakawa, Masaru Tanokura
In the last two decades, a wealth of structural and functional knowledge has been obtained for the three major cytoskeletal motor proteins, myosin, kinesin and dynein, which we review here. The cytoskeletal motor proteins myosin and kinesin are structurally similar in the core architecture of their motor domains and have similar force-producing mechanisms that are coupled with the chemical cycles of ATP binding, hydrolysis, Pi release and subsequent ADP release. The force is generated through conformational changes in the motor domain during Pi release and ATP binding in myosin and kinesin, respectively, and then converted into the rotation of the lever arm or neck linker (referred to as a power stroke) through the common structural pathways...
December 12, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/29217769/structural-insights-into-ankyrin-repeat-mediated-recognition-of-the-kinesin-motor-protein-kif21a-by-kank1-a-scaffold-protein-in-focal-adhesion
#12
Wenfei Pan, Kang Sun, Kun Tang, Qingpin Xiao, Chenxue Ma, Cong Yu, Zhiyi Wei
Kidney ankyrin repeat-containing proteins (KANK1/2/3/4) belong to a family of scaffold proteins, playing critical roles in cytoskeleton organization, cell polarity and migration. Mutations in KANK proteins are implicated in cancers and genetic diseases, such as nephrotic syndrome. KANK proteins can bind various target proteins through different protein regions, including a highly conserved ankyrin repeat domain (ANKRD). However, the molecular basis for target recognition by the ANKRD remains elusive. In this study, we solved a high-resolution crystal structure of the ANKRD of KANK1 in complex with a short sequence of the motor protein kinesin family member 21A (KIF21A), revealing that the highly specific target-binding mode of the ANKRD involves combinatorial use of two interfaces...
December 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29211997/challenges-in-estimating-the-motility-parameters-of-single-processive-motor-proteins
#13
Felix Ruhnow, Linda Kloβ, Stefan Diez
Cytoskeletal motor proteins are essential to the function of a wide range of intracellular mechano-systems. The biophysical characterization of their movement along their filamentous tracks is therefore of large importance. Toward this end, single-molecule, in vitro stepping-motility assays are commonly used to determine motor velocity and run length. However, comparing results from such experiments has proved difficult due to influences from variations in the experimental conditions and the data analysis methods...
December 5, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29204984/kinesin-kif4a-is-associated-with-chemotherapeutic-drug-resistance-by-regulating-intracellular-trafficking-of-lung-resistance-related-protein
#14
Li-Na Pan, Yuan Zhang, Chang-Jun Zhu, Zhi-Xiong Dong
Multidrug resistance (MDR) is the major impediment to cancer chemotherapy. The expression of lung resistance-related protein (LRP), a non-ATP-binding cassette (ABC) transporter, is high in tumor cells, resulting in their resistance to a variety of cytotoxic drugs. However, the function of LRP in tumor drug resistance is not yet explicit. Our previous studies had shown that Kinesin KIF4A was overexpressed in cisplatin (DDP)-resistant human lung adenocarcinoma cells (A549/DDP cells) compared with A549 cells. The expression of KIF4A in A549 or A549/DDP cells significantly affects cisplatin resistance but the detailed mechanisms remain unclear...
2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/29198755/differentiation-between-oppositely-oriented-microtubules-controls-polarized-neuronal-transport
#15
Roderick P Tas, Anaël Chazeau, Bas M C Cloin, Maaike L A Lambers, Casper C Hoogenraad, Lukas C Kapitein
Microtubules are essential for polarized transport in neurons, but how their organization guides motor proteins to axons or dendrites is unclear. Because different motors recognize distinct microtubule properties, we used optical nanoscopy to examine the relationship between microtubule orientations, stability, and modifications. Nanometric tracking of motors to super-resolve microtubules and determine their polarity revealed that in dendrites, stable and acetylated microtubules are mostly oriented minus-end out, while dynamic and tyrosinated microtubules are oriented oppositely...
November 28, 2017: Neuron
https://www.readbyqxmd.com/read/29196473/cell-scientist-to-watch-lukas-kapitein
#16
(no author information available yet)
Lukas Kapitein studied physics at the VU University in Amsterdam and graduated with a master's degree in experimental physics. He went on to do his PhD in the research groups of Christoph Schmidt and Erwin Peterman on the motility of mitotic kinesins, and in 2007, he won the biannual best thesis award from the Dutch society for Biophysics and Biomedical Technology. Lukas then joined the laboratory of Casper Hoogenraad at the Erasmus Medical Center in Rotterdam to work on the cytoskeleton and polarised cargo transport in neurons...
December 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29190901/kif11-is-required-for-proliferation-and-self-renewal-of-docetaxel-resistant-triple-negative-breast-cancer-cells
#17
Meng Jiang, Huiru Zhuang, Rui Xia, Lei Gan, Yuantao Wu, Junzhe Ma, Yihui Sun, Zhixiang Zhuang
Development of chemoresistance remains a major hurdle for triple negative breast cancer treatment. Previous studies suggest that CD44+/CD24- cells, subpopulation of cancer stem cells with self-renewing and tumor-initiating capacities, are partly responsible for chemoresistance and therapeutic failure of triple negative breast cancer. Therefore, novel agents that target cancer stem cells (CSCs) may improve the clinical outcome. KIF11 (kinesin family member 11), overexpressed in many cancer cells, is a molecular motor protein that plays essential role in mitosis...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163849/the-therapeutic-potential-of-cell-cycle-targeting-in-multiple-myeloma
#18
REVIEW
Anke Maes, Eline Menu, Kim De Veirman, Ken Maes, Karin Vand Erkerken, Elke De Bruyne
Proper cell cycle progression through the interphase and mitosis is regulated by coordinated activation of important cell cycle proteins (including cyclin-dependent kinases and mitotic kinases) and several checkpoint pathways. Aberrant activity of these cell cycle proteins and checkpoint pathways results in deregulation of cell cycle progression, which is one of the key hallmarks of cancer. Consequently, intensive research on targeting these cell cycle regulatory proteins identified several candidate small molecule inhibitors that are able to induce cell cycle arrest and even apoptosis in cancer cells...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29159770/jip3-localises-to-exocytic-vesicles-and-focal-adhesions-in-the-growth-cones-of-differentiated-pc12-cells
#19
Patrick T Caswell, Martin Dickens
The JNK-interacting protein 3 (JIP3) is a molecular scaffold, expressed predominantly in neurons, that serves to coordinate the activation of the c-Jun N-terminal kinase (JNK) by binding to JNK and the upstream kinases involved in its activation. The JNK pathway is involved in the regulation of many cellular processes including the control of cell survival, cell death and differentiation. JIP3 also associates with microtubule motor proteins such as kinesin and dynein and is likely an adapter protein involved in the tethering of vesicular cargoes to the motors involved in axonal transport in neurons...
November 20, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29158401/kinesin-dependent-mechanism-for-controlling-triglyceride-secretion-from-the-liver
#20
Priyanka Rai, Mukesh Kumar, Geetika Sharma, Pradeep Barak, Saumitra Das, Siddhesh S Kamat, Roop Mallik
Despite massive fluctuations in its internal triglyceride content, the liver secretes triglyceride under tight homeostatic control. This buffering function is most visible after fasting, when liver triglyceride increases manyfold but circulating serum triglyceride barely fluctuates. How the liver controls triglyceride secretion is unknown, but is fundamentally important for lipid and energy homeostasis in animals. Here we find an unexpected cellular and molecular mechanism behind such control. We show that kinesin motors are recruited to triglyceride-rich lipid droplets (LDs) in the liver by the GTPase ARF1, which is a key activator of lipolysis...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
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