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Kinesin-1

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https://www.readbyqxmd.com/read/27920150/heterotrimeric-kinesin-2-together-with-kinesin-1-steers-vesicular-acetylcholinesterase-movements-toward-the-synapse
#1
Anuttama Kulkarni, Yasmin Khan, Krishanu Ray
Acetylcholinesterase (AChE), which is implicated in the pathophysiology of neurological disorders, is distributed along the axon and enriched at the presynaptic basal lamina. It hydrolyses the neurotransmitter acetylcholine, which inhibits synaptic transmission. Aberrant AChE activity and ectopic axonal accumulation of the enzyme are associated with neurodegenerative disorders, such as Alzheimer's disease. The molecular mechanism that underlies AChE transport is still unclear. Here, we show that expression of Drosophila AChE tagged with photoactivable green fluorescent protein and m-Cherry (GPAC) in cholinergic neurons compensates for the RNA interference-mediated knockdown of endogenous AChE activity...
December 5, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27891669/a-molecular-dynamics-study-of-the-binary-complexes-of-app-jip1-and-the-cargo-binding-domain-of-klc
#2
Cooper A Taylor, Bill R Miller, Soleil S Shah, Carol A Parish
Mutations in the amyloid precursor protein (APP) are responsible for the formation of amyloid-β peptides. These peptides play a role in Alzheimer's and other dementia-related diseases. The cargo binding domain of the kinesin-1 light chain motor protein (KLC1) may be responsible for transporting APP either directly or via interaction with C-jun N-terminal kinase-interacting protein 1 (JIP1). However, to date there has been no direct experimental or computational assessment of such binding at the atomistic level...
November 7, 2016: Proteins
https://www.readbyqxmd.com/read/27851960/borc-functions-upstream-of-kinesins-1-and-3-to-coordinate-regional-movement-of-lysosomes-along-different-microtubule-tracks
#3
Carlos M Guardia, Ginny G Farías, Rui Jia, Jing Pu, Juan S Bonifacino
The multiple functions of lysosomes are critically dependent on their ability to undergo bidirectional movement along microtubules between the center and the periphery of the cell. Centrifugal and centripetal movement of lysosomes is mediated by kinesin and dynein motors, respectively. We recently described a multi-subunit complex named BORC that recruits the small GTPase Arl8 to lysosomes to promote their kinesin-dependent movement toward the cell periphery. Here, we show that BORC and Arl8 function upstream of two structurally distinct kinesin types: kinesin-1 (KIF5B) and kinesin-3 (KIF1Bβ and KIF1A)...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27821845/kinesin-1-motors-can-increase-the-lifetime-of-taxol-stabilized-microtubules
#4
Cordula Reuther, Alejandra Laguillo Diego, Stefan Diez
No abstract text is available yet for this article.
November 8, 2016: Nature Nanotechnology
https://www.readbyqxmd.com/read/27810912/kinesin-1-controls-mast-cell-degranulation-and-anaphylaxis-through-pi3k-dependent-recruitment-to-the-granular-slp3-rab27b-complex
#5
Isabelle Munoz, Luca Danelli, Julien Claver, Nicolas Goudin, Mathieu Kurowska, Iris Karina Madera-Salcedo, Jian-Dong Huang, Alain Fischer, Claudia González-Espinosa, Geneviéve de Saint Basile, Ulrich Blank, Gaël Ménasché
Cross-linking of mast cell (MC) IgE receptors (FcεRI) triggers degranulation of secretory granules (SGs) and the release of many allergic and inflammatory mediators. Although degranulation depends crucially on microtubule dynamics, the molecular machinery that couples SGs to microtubule-dependent transport is poorly understood. In this study, we demonstrate that mice lacking Kif5b (the heavy chain of kinesin-1) in hematopoietic cells are less sensitive to IgE-mediated, passive, systemic anaphylaxis. After IgE-induced stimulation, bone marrow-derived MCs from Kif5b knockout mice exhibited a marked reduction in SG translocation toward the secretion site...
October 24, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27803325/transport-efficiency-of-membrane-anchored-kinesin-1-motors-depends-on-motor-density-and-diffusivity
#6
Rahul Grover, Janine Fischer, Friedrich W Schwarz, Wilhelm J Walter, Petra Schwille, Stefan Diez
In eukaryotic cells, membranous vesicles and organelles are transported by ensembles of motor proteins. These motors, such as kinesin-1, have been well characterized in vitro as single molecules or as ensembles rigidly attached to nonbiological substrates. However, the collective transport by membrane-anchored motors, that is, motors attached to a fluid lipid bilayer, is poorly understood. Here, we investigate the influence of motors' anchorage to a lipid bilayer on the collective transport characteristics...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27802167/a-new-isoform-of-drosophila-non-muscle-tropomyosin-1-interacts-with-kinesin-1-and-functions-in-oskar-mrna-localization
#7
Rajalakshmi Veeranan-Karmegam, Devi Prasad Boggupalli, Guojun Liu, Graydon B Gonsalvez
Recent studies have revealed that diverse cell types use mRNA localization as a means to establish polarity. Despite the prevalence of this phenomenon, much less is known regarding the mechanism by which mRNAs are localized. The Drosophila melanogaster oocyte provides a useful model for examining the process of mRNA localization. oskar (osk) mRNA is localized at the posterior of the oocyte, thus restricting the expression of Oskar protein to this site. The localization of osk mRNA is microtubule dependent and requires the plus-end-directed motor Kinesin-1...
November 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27793291/interferometric-scattering-microscopy-for-the-study-of-molecular-motors
#8
J Andrecka, Y Takagi, K J Mickolajczyk, L G Lippert, J R Sellers, W O Hancock, Y E Goldman, P Kukura
Our understanding of molecular motor function has been greatly improved by the development of imaging modalities, which enable real-time observation of their motion at the single-molecule level. Here, we describe the use of a new method, interferometric scattering microscopy, for the investigation of motor protein dynamics by attaching and tracking the motion of metallic nanoparticle labels as small as 20nm diameter. Using myosin-5, kinesin-1, and dynein as examples, we describe the basic assays, labeling strategies, and principles of data analysis...
2016: Methods in Enzymology
https://www.readbyqxmd.com/read/27760367/the-effect-of-temperature-on-microtubule-based-transport-by-cytoplasmic-dynein-and-kinesin-1-motors
#9
Weili Hong, Anjneya Takshak, Olaolu Osunbayo, Ambarish Kunwar, Michael Vershinin
No abstract text is available yet for this article.
October 18, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27751944/hippocampal-to-basal-forebrain-transport-of-mn-2-is-impaired-by-deletion-of-klc1-a-subunit-of-the-conventional-kinesin-microtubule-based-motor
#10
Christopher S Medina, Octavian Biris, Tomas L Falzone, Xiaowei Zhang, Amber J Zimmerman, Elaine L Bearer
Microtubule-based motors carry cargo back and forth between the synaptic region and the cell body. Defects in axonal transport result in peripheral neuropathies, some of which are caused by mutations in KIF5A, a gene encoding one of the heavy chain isoforms of conventional kinesin-1. Some mutations in KIF5A also cause severe central nervous system defects in humans. While transport dynamics in the peripheral nervous system have been well characterized experimentally, transport in the central nervous system is less experimentally accessible and until now not well described...
October 14, 2016: NeuroImage
https://www.readbyqxmd.com/read/27729532/working-stroke-of-the-kinesin-14-ncd-comprises-two-substeps-of-different-direction
#11
Bert Nitzsche, Elzbieta Dudek, Lukasz Hajdo, Andrzej A Kasprzak, Andrej Vilfan, Stefan Diez
Single-molecule experiments have been used with great success to explore the mechanochemical cycles of processive motor proteins such as kinesin-1, but it has proven difficult to apply these approaches to nonprocessive motors. Therefore, the mechanochemical cycle of kinesin-14 (ncd) is still under debate. Here, we use the readout from the collective activity of multiple motors to derive information about the mechanochemical cycle of individual ncd motors. In gliding motility assays we performed 3D imaging based on fluorescence interference contrast microscopy combined with nanometer tracking to simultaneously study the translation and rotation of microtubules...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27697906/nuclei-migrate-through-constricted-spaces-using-microtubule-motors-and-actin-networks-in-c-elegans-hypodermal-cells
#12
Courtney R Bone, Yu-Tai Chang, Natalie E Cain, Shaun P Murphy, Daniel A Starr
Cellular migrations through constricted spaces are a crucial aspect of many developmental and disease processes including hematopoiesis, inflammation and metastasis. A limiting factor in these events is nuclear deformation. Here, we establish an in vivo model in which nuclei can be visualized while moving through constrictions and use it to elucidate mechanisms for nuclear migration. C. elegans hypodermal P-cell larval nuclei traverse a narrow space that is about 5% their width. This constriction is blocked by fibrous organelles, structures that pass through P cells to connect the muscles to cuticle...
November 15, 2016: Development
https://www.readbyqxmd.com/read/27629715/soluble-conformers-of-a%C3%AE-and-tau-alter-selective-proteins-governing-axonal-transport
#13
Mathew A Sherman, Michael LaCroix, Fatou Amar, Megan E Larson, Colleen Forster, Adriano Aguzzi, David A Bennett, Martin Ramsden, Sylvain E Lesné
UNLABELLED: Despite the demonstration that amyloid-β (Aβ) can trigger increased tau phosphorylation and neurofibrillary tangle (NFT) formation in vivo, the molecular link associating Aβ and tau pathologies remains ill defined. Here, we observed that exposure of cultured primary neurons to Aβ trimers isolated from brain tissue of subjects with Alzheimer's disease led to a specific conformational change of tau detected by the antibody Alz50. A similar association was supported by postmortem human brain analyses...
September 14, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27564000/discrete-step-sizes-of-molecular-motors-lead-to-bimodal-non-gaussian-velocity-distributions-under-force
#14
Huong T Vu, Shaon Chakrabarti, Michael Hinczewski, D Thirumalai
Fluctuations in the physical properties of biological machines are inextricably linked to their functions. Distributions of run lengths and velocities of processive molecular motors, like kinesin-1, are accessible through single-molecule techniques, but rigorous theoretical models for these probabilities are lacking. Here, we derive exact analytic results for a kinetic model to predict the resistive force (F)-dependent velocity [P(v)] and run length [P(n)] distribution functions of generic finitely processive molecular motors...
August 12, 2016: Physical Review Letters
https://www.readbyqxmd.com/read/27563844/co-delivery-of-cell-wall-forming-enzymes-in-the-same-vesicle-for-coordinated-fungal-cell-wall-formation
#15
Martin Schuster, Magdalena Martin-Urdiroz, Yujiro Higuchi, Christian Hacker, Sreedhar Kilaru, Sarah J Gurr, Gero Steinberg
Fungal cells are surrounded by an extracellular cell wall. This complex matrix of proteins and polysaccharides protects against adverse stresses and determines the shape of fungal cells. The polysaccharides of the fungal wall include 1,3-β-glucan and chitin, which are synthesized by membrane-bound synthases at the growing cell tip. A hallmark of filamentous fungi is the class V chitin synthase, which carries a myosin-motor domain. In the corn smut fungus Ustilago maydis, the myosin-chitin synthase Mcs1 moves to the plasma membrane in secretory vesicles, being delivered by kinesin-1 and myosin-5...
2016: Nature Microbiology
https://www.readbyqxmd.com/read/27512046/role-of-kinesin-1-based-microtubule-sliding-in-drosophila-nervous-system-development
#16
Michael Winding, Michael T Kelliher, Wen Lu, Jill Wildonger, Vladimir I Gelfand
The plus-end microtubule (MT) motor kinesin-1 is essential for normal development, with key roles in the nervous system. Kinesin-1 drives axonal transport of membrane cargoes to fulfill the metabolic needs of neurons and maintain synapses. We have previously demonstrated that kinesin-1, in addition to its well-established role in organelle transport, can drive MT-MT sliding by transporting "cargo" MTs along "track" MTs, resulting in dramatic cell shape changes. The mechanism and physiological relevance of this MT sliding are unclear...
August 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27512034/microtubule-microtubule-sliding-by-kinesin-1-is-essential-for-normal-cytoplasmic-streaming-in-drosophila-oocytes
#17
Wen Lu, Michael Winding, Margot Lakonishok, Jill Wildonger, Vladimir I Gelfand
Cytoplasmic streaming in Drosophila oocytes is a microtubule-based bulk cytoplasmic movement. Streaming efficiently circulates and localizes mRNAs and proteins deposited by the nurse cells across the oocyte. This movement is driven by kinesin-1, a major microtubule motor. Recently, we have shown that kinesin-1 heavy chain (KHC) can transport one microtubule on another microtubule, thus driving microtubule-microtubule sliding in multiple cell types. To study the role of microtubule sliding in oocyte cytoplasmic streaming, we used a Khc mutant that is deficient in microtubule sliding but able to transport a majority of cargoes...
August 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27505885/kinesin-1-sorting-in-axons-controls-the-differential-retraction-of-arbor-terminals
#18
Takeshi Seno, Tatsuki Ikeno, Kousuke Mennya, Masayuki Kurishita, Narumi Sakae, Makoto Sato, Hiroki Takada, Yoshiyuki Konishi
The ability of neurons to generate multiple arbor terminals from a single axon is crucial for establishing proper neuronal wiring. Although growth and retraction of arbor terminals are differentially regulated within the axon, the mechanisms by which neurons locally control their structure remain largely unknown. In the present study, we found that the kinesin-1 (Kif5 proteins) head domain (K5H) preferentially marks a subset of arbor terminals. Time-lapse imaging clarified that these arbor terminals were more stable than others, because of a low retraction rate...
September 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27503105/the-contribution-of-the-c-terminal-tails-of-microtubules-in-altering-the-force-production-specifications-of-multiple-kinesin-1
#19
Mitra Shojania Feizabadi
The extent to which beta tubulin isotypes contribute to the function of microtubules and the microtubule-driven transport of molecular motors is poorly understood. The major differences in these isotypes are associated with the structure of their C-terminal tails. Recent studies have revealed a few aspects of the C-terminal tails' regulatory role on the activities of some of the motor proteins on a single-molecule level. However, little attention is given to the degree to which the function of a team of motor proteins can be altered by the microtubule's tail...
September 2016: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27494025/strain-mediated-adaptation-is-key-for-myosin-mechanochemistry-discovering-general-rules-for-motor-activity
#20
Biman Jana, José N Onuchic
A structure-based model of myosin motor is built in the same spirit of our early work for kinesin-1 and Ncd towards physical understanding of its mechanochemical cycle. We find a structural adaptation of the motor head domain in post-powerstroke state that signals faster ADP release from it compared to the same from the motor head in the pre-powerstroke state. For dimeric myosin, an additional forward strain on the trailing head, originating from the postponed powerstroke state of the leading head in the waiting state of myosin, further increases the rate of ADP release...
August 2016: PLoS Computational Biology
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