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Kinesin-1

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https://www.readbyqxmd.com/read/28636917/kinesin-processivity-is-determined-by-a-kinetic-race-from-a-vulnerable-one-head-bound-state
#1
Keith J Mickolajczyk, William O Hancock
Kinesin processivity, defined as the average number of steps that occur per interaction with a microtubule, is an important biophysical determinant of the motor's intracellular capabilities. Despite its fundamental importance to the diversity of tasks that kinesins carry out in cells, no existing quantitative model fully explains how structural differences between kinesins alter kinetic rates in the ATPase cycle to produce functional changes in processivity. Here we use high-resolution single-molecule microscopy to directly observe the stepping behavior of kinesin-1 and -2 family motors with different length neck-linker domains...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28631604/vaccinia-virus-egress-mediated-by-virus-protein-a36-is-reliant-on-the-f12-protein
#2
David C J Carpentier, Alexander Van Loggerenberg, Nele M G Dieckmann, Geoffrey L Smith
Egress of vaccinia virus from its host cell is mediated by the microtubule-associated motor kinesin-1, and three viral proteins, A36 and the F12/E2 complex, have been implicated in this process. Deletion of F12 expression causes a more severe reduction in egress than deletion of A36 but whether these proteins are involved in the same or different mechanisms of kinesin-1 recruitment is unknown. Here it is shown that a virus lacking both proteins forms a smaller plaque than mutants lacking either gene alone, indicating non-redundant functions...
June 20, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28620116/kinesin-1-does-not-transport-melanosomes
#3
(no author information available yet)
No abstract text is available yet for this article.
June 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28537258/exploiting-the-kinesin-1-molecular-motor-to-generate-a-virus-membrane-penetration-site
#4
Madhu Sudhan Ravindran, Martin F Engelke, Kristen J Verhey, Billy Tsai
Viruses exploit cellular machineries to penetrate a host membrane and cause infection, a process that remains enigmatic for non-enveloped viruses. Here we probe how the non-enveloped polyomavirus SV40 penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol, a crucial infection step. We find that the microtubule-based motor kinesin-1 is recruited to the ER membrane by binding to the transmembrane J-protein B14. Strikingly, this motor facilitates SV40 ER-to-cytosol transport by constructing a penetration site on the ER membrane called a 'focus'...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28533284/nesprin-1%C3%AE-2-is-essential-for-mouse-postnatal-viability-and-nuclear-positioning-in-skeletal-muscle
#5
Matthew J Stroud, Wei Feng, Jianlin Zhang, Jennifer Veevers, Xi Fang, Larry Gerace, Ju Chen
The position of the nucleus in a cell is controlled by interactions between the linker of nucleoskeleton and cytoskeleton (LINC) complex and the cytoskeleton. Defects in nuclear positioning and abnormal aggregation of nuclei occur in many muscle diseases and correlate with muscle dysfunction. Nesprin 1, which includes multiple isoforms, is an integral component of the LINC complex, critical for nuclear positioning and anchorage in skeletal muscle, and is thought to provide an essential link between nuclei and actin...
May 22, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28505371/the-arm-domain-of-armadillo-repeat-kinesin-1-is-not-required-for-microtubule-catastrophe-but-can-negatively-regulate-nima-related-kinase-6-in-arabidopsis-thaliana
#6
Ryan C Eng, Laryssa S Halat, Samuel J Livingston, Tatsuya Sakai, Hiroyasu Motose, Geoffrey Wasteneys
Microtubules are dynamic filaments, the assembly and disassembly of which are under precise control of various associated proteins, including motor proteins and regulatory enzymes. In Arabidopsis thaliana, two such proteins are the ARMADILLO-REPEAT KINESIN 1 (ARK1), which promotes microtubule disassembly, and the NIMA-RELATED KINASE 6 (NEK6), which has a role in organizing microtubule arrays. Previous yeast 2-hybrid and in vitro pull-down assays determined that NEK6 can interact with ARK1 through the latter protein's Armadillo-repeat (ARM) cargo domain...
May 13, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28490438/deficiency-in-kinesin-1-recruitment-to-melanosomes-precludes-it-from-facilitating-their-centrifugal-transport
#7
Christopher L Robinson, Richard D Evans, Deborah A Briggs, Jose S Ramalho, Alistair N Hume
Microtubules and F-actin, and associated motor proteins, are considered to play complementary roles in long- and short-range organelle transport. However, there is growing appreciation that myosin/F-actin networks can drive long-range transport. In melanocytes myosin-Va and kinesin-1 have both been proposed as long-range centrifugal melanosome transporters. Here we investigated the role of kinesin-1 heavy chain (Kif5b) and its suggested targeting factor Rab1a in transport. Using confocal microscopy and sub-cellular fractionation we did not detect Kif5b or Rab1a on melanosomes...
May 10, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28485852/vaccinia-virus-proteins-a36-and-f12-e2-show-strong-preferences-for-different-klc-isoforms
#8
William N D Gao, David C J Carpentier, Helen A Ewles, Stacey-Ann Lee, Geoffrey L Smith
Vaccinia virus (VACV) utilises microtubule-mediated trafficking at several stages of its life cycle, of which virus egress is the most intensely studied. During egress VACV proteins A36, F12 and E2 are involved in kinesin-1 interactions, however the roles of these proteins remain poorly understood. A36 forms a direct link between virions and kinesin-1, yet in its absence VACV egress still occurs on microtubules. During a co-immunoprecipitation screen to seek an alternative link between virions and kinesin, A36 was found to bind isoform KLC1 rather than KLC2...
May 9, 2017: Traffic
https://www.readbyqxmd.com/read/28484025/common-general-anesthetic-propofol-impairs-kinesin-processivity
#9
Brandon M Bensel, Stephanie Guzik-Lendrum, Erin M Masucci, Kellie A Woll, Roderic G Eckenhoff, Susan P Gilbert
Propofol is the most widely used i.v. general anesthetic to induce and maintain anesthesia. It is now recognized that this small molecule influences ligand-gated channels, including the GABAA receptor and others. Specific propofol binding sites have been mapped using photoaffinity ligands and mutagenesis; however, their precise target interaction profiles fail to provide complete mechanistic underpinnings for the anesthetic state. These results suggest that propofol and other common anesthetics, such as etomidate and ketamine, may target additional protein networks of the CNS to contribute to the desired and undesired anesthesia end points...
May 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28426968/map2-defines-a-pre-axonal-filtering-zone-to-regulate-kif1-versus-kif5-dependent-cargo-transport-in-sensory-neurons
#10
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
#11
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
#12
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 7, 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
#13
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
#14
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
#15
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 (also known as PLEKHM2) as model cargo, we show that the kinesin heavy chains (KHCs), in addition to the kinesin 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 However, in the absence of KLCs, SKIP can only bind to KHC when autoinhibition is relieved, suggesting that the KLCs gate access to the KHCs...
May 1, 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
#16
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
#17
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
#18
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
#19
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...
July 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28267922/tetrazine-trans-cyclooctene-mediated-conjugation-of-antibodies-to-microtubules-facilitates-subpicomolar-protein-detection
#20
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...
April 19, 2017: Bioconjugate Chemistry
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