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Kinesin-1

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https://www.readbyqxmd.com/read/28720664/dynein-efficiently-navigates-the-dendritic-cytoskeleton-to-drive-the-retrograde-trafficking-of-bdnf-trkb-signaling-endosomes
#1
Swathi Ayloo, Pedro Guedes-Dias, Amy E Ghiretti, Erika L F Holzbaur
The efficient transport of cargoes within axons and dendrites is critical for neuronal function. While we have a basic understanding of axonal transport, much less is known about transport in dendrites. We employed an optogenetic approach to recruit motor proteins to cargo in real time within axons or dendrites in hippocampal neurons. Kinesin-1, a robust axonal motor, moves cargo less efficiently in dendrites. In contrast, cytoplasmic dynein efficiently navigates both axons and dendrites; in both compartments, dynamic microtubule plus-ends enhance dynein-dependent transport...
July 18, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28715414/kinesin-1-promotes-chondrocyte-maintenance-during-skeletal-morphogenesis
#2
Adrian Santos-Ledo, Marina Garcia-Macia, Philip D Campbell, Marta Gronska, Florence L Marlow
During skeletal morphogenesis diverse mechanisms are used to support bone formation. This can be seen in the bones that require a cartilage template for their development. In mammals the cartilage template is removed, but in zebrafish the cartilage template persists and the bone mineralizes around the cartilage scaffold. Remodeling of unmineralized cartilage occurs via planar cell polarity (PCP) mediated cell rearrangements that contribute to lengthening of elements; however, the mechanisms that maintain the chondrocyte template that supports perichondral ossification remain unclear...
July 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28699205/native-kinesin-1-does-not-bind-preferentially-to-gtp-tubulin-rich-microtubules-in-vitro
#3
Qiaochu Li, Stephen J King, Jing Xu
Molecular motors such as kinesin-1 work in small teams to actively shuttle cargos in cells, for example in polarized transport in axons. Here we examined the potential regulatory role of the nucleotide state of tubulin on the run length of cargos carried by multiple kinesin motors, using an optical trapping-based in vitro assay. Based on a previous report that kinesin binds preferentially to GTP-tubulin-rich microtubules, we anticipated that multiple-kinesin cargos would run substantially greater distances along GMPCPP microtubules than along GDP microtubules...
July 12, 2017: Cytoskeleton
https://www.readbyqxmd.com/read/28678816/characterization-of-kinesin-switch-i-mutations-that-cause-hereditary-spastic-paraplegia
#4
Scott Jennings, Madeline Chenevert, Liqiong Liu, Madhusoodanan Mottamal, Edward J Wojcik, Thomas M Huckaba
Kif5A is a neuronally-enriched isoform of the Kinesin-1 family of cellular transport motors. 23 separate mutations in the motor domain of Kif5A have been identified in patients with the complicated form of hereditary spastic paraplegia (HSP). We performed in vitro assays on dimeric recombinant Kif5A with HSP-causing mutations in the Switch I domain, which participates in the coordination and hydrolysis of ATP by kinesin. We observed a variety of significantly reduced catalytic and mechanical activities as a result of each mutation, with the shared phenotype from each that motility was significantly reduced...
2017: PloS One
https://www.readbyqxmd.com/read/28663865/multimodal-nonlinear-optical-microscopy-reveals-critical-role-of-kinesin-1-in-cartilage-development
#5
Sicong He, Wenqian Xue, Zhigang Duan, Qiqi Sun, Xuesong Li, Huiyan Gan, Jiandong Huang, Jianan Y Qu
We developed a multimodal nonlinear optical (NLO) microscope system by integrating stimulated Raman scattering (SRS), second harmonic generation (SHG) and two-photon excited fluorescence (TPEF) imaging. The system was used to study the morphological and biochemical characteristics of tibial cartilage in a kinesin-1 (Kif5b) knockout mouse model. The detailed structure of fibrillar collagen in the extracellular matrix of cartilage was visualized by the forward and backward SHG signals, while high resolution imaging of chondrocytes was achieved by capturing endogenous TPEF and SRS signals of the cells...
March 1, 2017: Biomedical Optics Express
https://www.readbyqxmd.com/read/28638935/jip1-and-jip3-cooperate-to-mediate-trkb-anterograde-axonal-transport-by-activating-kinesin-1
#6
Tao Sun, Yuan Li, Ting Li, Huixian Ma, Yunyun Guo, Xingyu Jiang, Ming Hou, Shuhong Huang, Zheyu Chen
Long-range anterograde axonal transport of TrkB is important for neurons to exert appropriate BDNF responses. TrkB anterograde axonal delivery is mediated by kinesin-1, which associates with TrkB via the adaptor protein JIP3 or the Slp1/Rab27B/CRMP-2 protein complex. However, little is known about the activation mechanisms of TrkB-loaded kinesin-1. Here, we show that JIP1 mediates TrkB anterograde axonal transport using JIP1 knockout mice, sciatic nerve ligation analysis and live imaging. Next, we proved that JIP1 and JIP3 cooperate to mediate TrkB anterograde axonal transport...
June 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28637747/f-actin-prevents-interaction-between-sperm-dna-and-the-oocyte-meiotic-spindle-in-c-elegans
#7
Michelle T Panzica, Harold C Marin, Anne-Cecile Reymann, Francis J McNally
Fertilization occurs during female meiosis in most animals, which raises the question of what prevents the sperm DNA from interacting with the meiotic spindle. In this study, we find that Caenorhabditis elegans sperm DNA stays in a fixed position at the opposite end of the embryo from the meiotic spindle while yolk granules are transported throughout the embryo by kinesin-1. In the absence of F-actin, the sperm DNA, centrioles, and organelles were transported as a unit with the yolk granules, resulting in sperm DNA within 2 µm of the meiotic spindle...
June 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28636917/kinesin-processivity-is-determined-by-a-kinetic-race-from-a-vulnerable-one-head-bound-state
#8
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
#9
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 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28620116/kinesin-1-does-not-transport-melanosomes
#10
(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
#11
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
#12
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...
July 3, 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
#13
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/inefficient-recruitment-of-kinesin-1-to-melanosomes-precludes-it-from-facilitating-their-transport
#14
Christopher L Robinson, Richard D Evans, Deborah A Briggs, Jose S Ramalho, Alistair N Hume
Microtubules and F-actin, and their 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 transporters moving melanosomes into the peripheral dendrites. Here, we investigated the role of kinesin-1 heavy chain (Kif5b) and its suggested targeting factor Rab1a in transport...
June 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28485852/vaccinia-virus-proteins-a36-and-f12-e2-show-strong-preferences-for-different-kinesin-light-chain-isoforms
#15
William N D Gao, David C J Carpentier, Helen A Ewles, Stacey-Ann Lee, Geoffrey L Smith
Vaccinia virus (VACV) utilizes 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
#16
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
#17
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
#18
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
#19
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
#20
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
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