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Kinesin-1

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https://www.readbyqxmd.com/read/28426968/map2-defines-a-pre-axonal-filtering-zone-to-regulate-kif1-versus-kif5-dependent-cargo-transport-in-sensory-neurons
#1
Laura F Gumy, Eugene A Katrukha, Ilya Grigoriev, Dick Jaarsma, Lukas C Kapitein, Anna Akhmanova, Casper C Hoogenraad
Polarized cargo transport is essential for neuronal function. However, the minimal basic components required for selective cargo sorting and distribution in neurons remain elusive. We found that in sensory neurons the axon initial segment is largely absent and that microtubule-associated protein 2 (MAP2) defines the cargo-filtering zone in the proximal axon. Here, MAP2 directs axonal cargo entry by coordinating the activities of molecular motors. We show that distinct kinesins differentially regulate cargo velocity: kinesin-3 drives fast axonal cargo trafficking, while kinesin-1 slows down axonal cargo transport...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28393873/crystal-structure-of-zen4-in-the-apo-state-reveals-a-missing-conformation-of-kinesin
#2
Ruifang Guan, Lei Zhang, Qian Peter Su, Keith J Mickolajczyk, Geng-Yuan Chen, William O Hancock, Yujie Sun, Yongfang Zhao, Zhucheng Chen
Kinesins hydrolyse ATP to transport intracellular cargoes along microtubules. Kinesin neck linker (NL) functions as the central mechano-chemical coupling element by changing its conformation through the ATPase cycle. Here we report the crystal structure of kinesin-6 Zen4 in a nucleotide-free, apo state, with the NL initial segment (NIS) adopting a backward-docked conformation and the preceding α6 helix partially melted. Single-molecule fluorescence resonance energy transfer (smFRET) analyses indicate the NIS of kinesin-1 undergoes similar conformational changes under tension in the two-head bound (2HB) state, whereas it is largely disordered without tension...
April 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28392418/spastin-regulates-vamp7-containing-vesicles-trafficking-in-cortical-neurons
#3
C Plaud, V Joshi, M Marinello, D Pastré, T Galli, P A Curmi, A Burgo
Alteration of axonal transport has emerged as a common precipitating factor in several neurodegenerative disorders including Human Spastic Paraplegia (HSP). Mutations of the SPAST (SPG4) gene coding for the spastin protein account for 40% of all autosomal dominant uncomplicated HSP. By cleaving microtubules, spastin regulates several cellular processes depending on microtubule dynamics including intracellular membrane trafficking. Axonal transport is fundamental for the viability of motor neurons which often have very long axons and thus require efficient communication between the cell body and its periphery...
April 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28322225/probing-cytoskeletal-modulation-of-passive-and-active-intracellular-dynamics-using-nanobody-functionalized-quantum-dots
#4
Eugene A Katrukha, Marina Mikhaylova, Hugo X van Brakel, Paul M van Bergen En Henegouwen, Anna Akhmanova, Casper C Hoogenraad, Lukas C Kapitein
The cytoplasm is a highly complex and heterogeneous medium that is structured by the cytoskeleton. How local transport depends on the heterogeneous organization and dynamics of F-actin and microtubules is poorly understood. Here we use a novel delivery and functionalization strategy to utilize quantum dots (QDs) as probes for active and passive intracellular transport. Rapid imaging of non-functionalized QDs reveals two populations with a 100-fold difference in diffusion constant, with the faster fraction increasing upon actin depolymerization...
March 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28320970/borc-kinesin-1-ensemble-drives-polarized-transport-of-lysosomes-into-the-axon
#5
Ginny G Farías, Carlos M Guardia, Raffaella De Pace, Dylan J Britt, Juan S Bonifacino
The ability of lysosomes to move within the cytoplasm is important for many cellular functions. This ability is particularly critical in neurons, which comprise vast, highly differentiated domains such as the axon and dendrites. The mechanisms that control lysosome movement in these domains, however, remain poorly understood. Here we show that an ensemble of BORC, Arl8, SKIP, and kinesin-1, previously shown to mediate centrifugal transport of lysosomes in nonneuronal cells, specifically drives lysosome transport into the axon, and not the dendrites, in cultured rat hippocampal neurons...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28302907/skip-controls-lysosome-positioning-using-a-composite-kinesin-1-heavy-and-light-chain-binding-domain
#6
Anneri Sanger, Yan Y Yip, Thomas S Randall, Stefano Pernigo, Roberto A Steiner, Mark P Dodding
The molecular interplay between cargo recognition and regulation of the activity of the kinesin-1 microtubule motor is not well understood. Using the lysosome adaptor SKIP as model cargo, we show that the heavy chains (KHCs), in addition to the light chains (KLCs), can recognize tryptophan-acidic binding determinants on the cargo when presented in the context of an extended KHC interacting domain. Mutational separation of KHC and KLC binding shows that both interactions are important for SKIP-kinesin-1 interaction in vitro and that KHC binding is important for lysosome transport in vivo...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28300595/a-biophysical-model-of-how-%C3%AE-tubulin-carboxy-terminal-tails-tune-kinesin-1-processivity-along-microtubule
#7
Miljko V Sataric, Dalibor L Sekulic, Slobodan Zdravkovic, Nebojsa M Ralevic
It appears that so-called post-translational modifications of tubulin heterodimers are mostly focussed at positions of amino acid sequences of carboxy-terminal tails. These changes have very profound effects on microtubule functions especially in connection with cellular traffic in terms of motor proteins. In this study, we elaborated the biophysical model aimed to explain the strategy governing these subtle interplays between structural and functional properties of microtubules. We relied onto Langevin equations including fluctuation-dissipation processes...
March 12, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28298410/fus-inclusions-disrupt-rna-localization-by-sequestering-kinesin-1-and-inhibiting-microtubule-detyrosination
#8
Kyota Yasuda, Sarah F Clatterbuck-Soper, Meredith E Jackrel, James Shorter, Stavroula Mili
Cytoplasmic inclusions of the RNA-binding protein fused in sarcoma (FUS) represent one type of membraneless ribonucleoprotein compartment. Formation of FUS inclusions is promoted by amyotrophic lateral sclerosis (ALS)-linked mutations, but the cellular functions affected upon inclusion formation are poorly defined. In this study, we find that FUS inclusions lead to the mislocalization of specific RNAs from fibroblast cell protrusions and neuronal axons. This is mediated by recruitment of kinesin-1 mRNA and protein within FUS inclusions, leading to a loss of detyrosinated glutamate (Glu)-microtubules (MTs; Glu-MTs) and an inability to support the localization of RNAs at protrusions...
April 3, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28287156/single-molecule-investigation-of-kinesin-1-motility-using-engineered-microtubule-defects
#9
Michael W Gramlich, Leslie Conway, Winnie H Liang, Joelle A Labastide, Stephen J King, Jing Xu, Jennifer L Ross
The structure of the microtubule is tightly regulated in cells via a number of microtubule associated proteins and enzymes. Microtubules accumulate structural defects during polymerization, and defect size can further increase under mechanical stresses. Intriguingly, microtubule defects have been shown to be targeted for removal via severing enzymes or self-repair. The cell's control in defect removal suggests that defects can impact microtubule-based processes, including molecular motor-based intracellular transport...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28284467/moonlighting-motors-kinesin-dynein-and-cell-polarity
#10
REVIEW
Wen Lu, Vladimir I Gelfand
In addition to their well-known role in transporting cargoes in the cytoplasm, microtubule motors organize their own tracks - the microtubules. While this function is mostly studied in the context of cell division, it is essential for microtubule organization and generation of cell polarity in interphase cells. Kinesin-1, the most abundant microtubule motor, plays a role in the initial formation of neurites. This review describes the mechanism of kinesin-1-driven microtubule sliding and discusses its biological significance in neurons...
March 8, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28267922/tetrazine-trans-cyclooctene-mediated-conjugation-of-antibodies-to-microtubules-facilitates-subpicomolar-protein-detection
#11
Samata Chaudhuri, Till Korten, Stefan Diez
Engineering cargo-loading strategies is crucial to developing nanotechnological applications of microtubule-based biomolecular transport systems. Here, we report a highly efficient and robust bioconjugation scheme to load antibodies to microtubules. Our method takes advantage of the inverse-electron-demand Diels-Alder addition reaction between tetrazine and trans-cyclooctene: the fastest known bioorthogonal reaction, characterized by its excellent selectivity and biocompatibility. As proof of concept, we performed kinesin-1 gliding motility assays with antibody-conjugated microtubules and demonstrated the highly sensitive detection of fluorescent protein analyte down to 0...
March 14, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28267259/the-axonal-transport-motor-kinesin-2-navigates-microtubule-obstacles-via-protofilament-switching
#12
Gregory J Hoeprich, Keith J Mickolajczyk, Shane R Nelson, William O Hancock, Christopher L Berger
Axonal transport involves kinesin motors trafficking cargo along microtubules that are rich in microtubule-associated proteins (MAPs). Much attention has focused on the behavior of kinesin-1 in the presence of MAPs, which has overshadowed understanding the contribution of other kinesins such as kinesin-2 in axonal transport. We have previously shown that, unlike kinesin-1, kinesin-2 in vitro motility is insensitive to the neuronal MAP Tau. However, the mechanism by which kinesin-2 efficiently navigates Tau on the microtubule surface is unknown...
March 7, 2017: Traffic
https://www.readbyqxmd.com/read/28251926/phosphoregulation-of-tau-modulates-inhibition-of-kinesin-1-motility
#13
Jamie L Stern, Dominique V Lessard, Gregory J Hoeprich, Gerardo A Morfini, Christopher L Berger
Microtubule-based axonal transport is tightly regulated by numerous pathways, ensuring appropriate delivery of specific organelle cargoes to selected subcellular domains. Highlighting the importance of this process, pathological evidence has linked alterations in these pathways to the pathogenesis of several neurodegenerative diseases. An important regulator of this system, the microtubule-associated protein Tau, has been shown to participate in signaling cascades, modulate microtubule dynamics, and preferentially inhibit kinesin-1 motility...
April 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28239703/the-effect-of-active-fluctuations-on-the-dynamics-of-particles-motors-and-dna-hairpins
#14
Hans Vandebroek, Carlo Vanderzande
Inspired by recent experiments on the dynamics of particles and polymers in artificial cytoskeletons and in cells, we introduce a modified Langevin equation for a particle in an environment that is a viscoelastic medium and that is brought out of equilibrium by the action of active fluctuations caused by molecular motors. We show that within such a model, the motion of a free particle crosses over from superdiffusive to subdiffusive as observed for tracer particles in an in vitro cytoskeleton or in a cell. We investigate the dynamics of a particle confined by a harmonic potential as a simple model for the motion of the tethered head of kinesin-1...
February 27, 2017: Soft Matter
https://www.readbyqxmd.com/read/28209731/transport-of-fungal-rab11-secretory-vesicles-involves-myosin-5-dynein-dynactin-p25-and-kinesin-1-and-is-independent-of-kinesin-3
#15
Miguel A Peñalva, Jun Zhang, Xin Xiang, Areti Pantazopoulou
Hyphal tip cells of the fungus Aspergillus nidulans are useful for studying long-range intracellular traffic. Post-Golgi secretory vesicles (SVs) containing the RAB11 orthologue RabE engage myosin-5 as well as plus end- and minus end-directed microtubule motors, providing an experimental system with which to investigate the interplay between microtubule and actin motors acting on the same cargo. By exploiting the fact that depolymerization of F-actin unleashes SVs focused at the apex by myosin-5 to microtubule-dependent motors, we establish that the minus end-directed transport of SVs requires the dynein/dynactin supercomplex...
April 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28195215/the-structural-switch-of-nucleotide-free-kinesin
#16
Luyan Cao, Soraya Cantos-Fernandes, Benoît Gigant
Kinesin-1 is an ATP-dependent motor protein that moves towards microtubules (+)-ends. Whereas structures of isolated ADP-kinesin and of complexes with tubulin of apo-kinesin and of ATP-like-kinesin are available, structural data on apo-kinesin-1 in the absence of tubulin are still missing, leaving the role of nucleotide release in the structural cycle unsettled. Here, we identified mutations in the kinesin nucleotide-binding P-loop motif that interfere with ADP binding. These mutations destabilize the P-loop (T87A mutant) or magnesium binding (T92V), highlighting a dual mechanism for nucleotide release...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28189052/a-novel-zea-mays-ssp-mexicana-l-myc-type-ice-like-transcription-factor-gene-zmmice1-enhances-freezing-tolerance-in-transgenic-arabidopsis-thaliana
#17
Xiang Lu, Lei Yang, Mengyuan Yu, Jianbin Lai, Chao Wang, David McNeil, Meixue Zhou, Chengwei Yang
The annual Zea mays ssp. mexicana L., a member of the teosinte group, is a close wild relative of maize and thus can be effectively used in maize improvement. In this study, an ICE-like gene, ZmmICE1, was isolated from a cDNA library of RNA-Seq from cold-treated seedling tissues of Zea mays ssp. mexicana L. The deduced protein of ZmmICE1 contains a highly conserved basic helix-loop-helix (bHLH) domain and C-terminal region of ICE-like proteins. The ZmmICE1 protein localizes to the nucleus and shows sumoylation when expressed in an Escherichia coli reconstitution system...
February 5, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28165699/eg5-inhibitors-have-contrasting-effects-on-microtubule-stability-and-metaphase-spindle-integrity
#18
Geng-Yuan Chen, You Jung Kang, A Sophia Gayek, Wiphu Youyen, Erkan Tüzel, Ryoma Ohi, William O Hancock
To uncover their contrasting mechanisms, antimitotic drugs that inhibit Eg5 (kinesin-5) were analyzed in mixed-motor gliding assays of kinesin-1 and Eg5 motors in which Eg5 "braking" dominates motility. Loop-5 inhibitors (monastrol, STLC, ispinesib, and filanesib) increased gliding speeds, consistent with inducing a weak-binding state in Eg5, whereas BRD9876 slowed gliding, consistent with locking Eg5 in a rigor state. Biochemical and single-molecule assays demonstrated that BRD9876 acts as an ATP- and ADP-competitive inhibitor with 4 nM KI...
February 22, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28123706/interaction-of-fun14-domain-containing-1-a-mitochondrial-outer-membrane-protein-with-kinesin-light-chain-1-via-the-tetratricopeptide-repeat-domain
#19
Won Hee Jang, Young Joo Jeong, Sun Hee Choi, Sang-Hwa Urm, Dae-Hyun Seog
Kinesin 1 is a member of the kinesin superfamily proteins (KIFs) of microtubule-dependent molecular motor proteins that transport organelles and protein complexes in cells. Kinesin 1 consists of a homo- or hetero-dimer of kinesin heavy chains (KHCs), often, although not always, associated with two kinesin light chains (KLCs). KLCs are non-motor proteins that associate with many different binding proteins and cargoes, but their binding partners have not yet been fully identified. In the present study, a yeast two-hybrid system was used to identify proteins that interact with the tetratricopeptide repeat (TPR) domain of KLC1...
January 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28122263/toxic-effects-of-zinc-ions-on-kinesin-potential-molecular-cause-of-impaired-intracellular-transport
#20
Konrad J Böhm
In healthy organisms the metabolism of the trace element zinc is well balanced. If this balance becomes destroyed the free zinc level might increase and cause toxic effects. The present study demonstrates that under definite conditions zinc ions are able to inhibit the ATPase activity of neuron-specific KIF5A (kinesin-1). Correspondingly, the motility activity of KIF5A also decreased. The inhibition rates have been found to depend on the magnesium ion concentration. Lowering the magnesium concentration weakens the inhibition...
February 15, 2017: Toxicology Letters
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