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kinesine motor protein

Arunika Das, Jeffry Cesario, Anna Maria Hinman, Janet K Jang, Kim S McKim
Bipolar spindle assembly occurs in the absence of centrosomes in the oocytes of most organisms. In the absence of centrosomes in Drosophila oocytes, we have proposed that the kinesin 6 Subito, a MKLP-2 homolog, is required for establishing spindle bipolarity and chromosome biorientation by assembling a robust central spindle during prometaphase I. Although the functions of the conserved motor domains of kinesins is well studied, less is known about the contribution of the poorly conserved N- and C- terminal domains to motor function...
March 7, 2018: G3: Genes—Genomes—Genetics
Bor Luen Tang
The small GTPase Miro is best known for its regulation of mitochondrial movement by engaging with the microtubule-based motor proteins kinesin and dynein. Very recent findings have now showed that Miro also targets peroxisomes and regulates microtubule-dependent peroxisome motility. Moreover, Miro recruits and stabilizes the myosin motor Myo19 at the mitochondria to enable actin-based mitochondria movement, which is important for mitochondrial segregation during mitosis. Miro thus has much broader functions that previously known, and these new findings may have important implications on disease pathology...
March 4, 2018: Cells
I A Kuznetsov, A V Kuznetsov
We develop a mathematical model that enables us to investigate possible mechanisms by which two primary markers of Alzheimer's disease (AD), extracellular amyloid plaques and intracellular tangles, may be related. Our model investigates the possibility that the decay of anterograde axonal transport of amyloid precursor protein (APP), caused by toxic tau aggregates, leads to decreased APP transport towards the synapse and APP accumulation in the soma. The developed model thus couples three processes: (i) slow axonal transport of tau, (ii) tau misfolding and agglomeration, which we simulated by using the Finke-Watzky model and (iii) fast axonal transport of APP...
February 2018: Proceedings. Mathematical, Physical, and Engineering Sciences
Andreas Nebenführ, Ram Dixit
Kinesins and myosins are motor proteins that can move actively along microtubules and actin filaments, respectively. Plants have evolved a unique set of motors that function as regulators and organizers of the cytoskeleton and as drivers of long-distance transport of various cellular components. Recent progress has established the full complement of motors encoded in plant genomes and has revealed valuable insights into the cellular functions of many kinesin and myosin isoforms. Interestingly, several of the motors were found to functionally connect the two cytoskeletal systems and thereby to coordinate their activities...
February 28, 2018: Annual Review of Plant Biology
Xiaolu Xu, Wilhelm J Walter, Qiong Liu, Isabel Machens, Peter Nick
Higher plants possess a large number of kinesins, but lack the minus-end directed dynein motors. However, the kinesin class XIV has strongly expanded, and minus-end directed motors from this class may have taken over functions of cytoplasmic dyneins. In this study, we address the functional aspects of a novel rice homologue of the Arabidopsis class-XIV kinesins ATK1 and ATK5. Since a loss-of-function rice mutant of this kinesin is not viable, the function was studied in tobacco BY-2 as heterologous system. OsDLK-GFP stably expressed in BY-2 cells decorates cortical microtubules, but also can shift into the nucleus of interphase cells...
February 26, 2018: Scientific Reports
Lu Zhou, Theresa Obhof, Karina Schneider, Michael Feldbrügge, G Ulrich Nienhaus, Jörg Kämper
In the phytopathogenic basidiomycete Ustilago maydis, the Num1 protein has a pivotal function in hyphal morphogenesis. Num1 functions as a core component of the spliceosome-associated Prp19/CDC5 complex (NTC). The interaction of Num1 with the kinesin motor Kin1 suggests a connection between a component of the splicing machinery and cytoplasmic trafficking processes. Previously it was shown that Num1 localizes predominantly in the nucleus; however, due to the diffraction-limited spatial resolution of conventional optical microscopy, it was not possible to attribute the localization to specific structures within the cytoplasm...
February 26, 2018: Scientific Reports
Rossina Novas, Magdalena Cardenas-Rodriguez, Paola Lepanto, Matías Fabregat, Magela Rodao, María Inés Fariello, Mauricio Ramos, Camila Davison, Gabriela Casanova, Lucía Alfaya, Federico Lecumberry, Gualberto González-Sapienza, Florencia Irigoín, Jose L Badano
Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinal degeneration, obesity, polydactyly, renal disease and mental retardation. CCDC28B is a BBS-associated protein that we have previously shown plays a role in cilia length regulation whereby its depletion results in shortened cilia both in cells and Danio rerio (zebrafish). At least part of that role is achieved by its interaction with the mTORC2 component SIN1, but the mechanistic details of this interaction and/or additional functions that CCDC28B might play in the context of cilia remain poorly understood...
February 14, 2018: Scientific Reports
Nathan L Hendel, Matthew Thomson, Wallace F Marshall
An important question in cell biology is whether cells are able to measure size, either whole cell size or organelle size. Perhaps cells have an internal chemical representation of size that can be used to precisely regulate growth, or perhaps size is just an accident that emerges due to constraint of nutrients. The eukaryotic flagellum is an ideal model for studying size sensing and control because its linear geometry makes it essentially one-dimensional, greatly simplifying mathematical modeling. The assembly of flagella is regulated by intraflagellar transport (IFT), in which kinesin motors carry cargo adaptors for flagellar proteins along the flagellum and then deposit them at the tip, lengthening the flagellum...
February 6, 2018: Biophysical Journal
Sudhir Kumar Singh, Himanshu Pandey, Jawdat Al-Bassam, Larisa Gheber
Mitotic kinesin-5 bipolar motor proteins perform essential functions in mitotic spindle dynamics by crosslinking and sliding antiparallel microtubules (MTs) apart within the mitotic spindle. Two recent studies have indicated that single molecules of Cin8, the Saccharomyces cerevisiae kinesin-5 homolog, are minus end-directed when moving on single MTs, yet switch directionality under certain experimental conditions (Gerson-Gurwitz et al., EMBO J 30:4942-4954, 2011; Roostalu et al., Science 332:94-99, 2011). This finding was unexpected since the Cin8 catalytic motor domain is located at the N-terminus of the protein, and such kinesins have been previously thought to be exclusively plus end-directed...
February 3, 2018: Cellular and Molecular Life Sciences: CMLS
Lu Zhou, Minoas Evangelinos, Valentin Wernet, Antonia F Eckert, Yuji Ishitsuka, Reinhard Fischer, G Ulrich Nienhaus, Norio Takeshita
Polarized growth of filamentous fungi requires continuous transport of biomolecules to the hyphal tip. To this end, construction materials are packaged in vesicles and transported by motor proteins along microtubules and actin filaments. We have studied these processes with quantitative superresolution localization microscopy of live Aspergillus nidulans cells expressing the photoconvertible protein mEosFPthermo fused to the chitin synthase ChsB. ChsB is mainly located at the Spitzenkörper near the hyphal tip and produces chitin, a key component of the cell wall...
January 2018: Science Advances
Helen Chen, Marisa Connell, Lin Mei, Gregor S D Reid, Christopher A Maxwell
Mitotic spindle assembly and organization require forces generated by motor proteins. The activity of these motors is regulated by non-motor adaptor proteins. However, there are limited studies reporting the functional importance of adaptors on the balance of motor forces and the promotion of faithful and timely cell division. Here, we show that genomic deletion or siRNA silencing of the non-motor adaptor Hmmr/HMMR disturbs spindle microtubule organization and bipolar chromosome-kinetochore attachments with a consequent elevated occurrence of aneuploidy...
January 31, 2018: Molecular Biology of the Cell
Michael Bugiel, Aniruddha Mitra, Salvatore Girardo, Stefan Diez, Erik Schäffer
Three-dimensional (3D) nanometer tracking of single biomolecules provides important information about their biological function. However, existing microscopy approaches often have only limited spatial or temporal precision and do not allow the application of defined loads. Here, we developed and applied a high-precision 3D-optical-tweezers force clamp to track in vitro the 3D motion of single kinesin-1 motor proteins along microtubules. To provide the motors with unimpeded access to the whole microtubule lattice, we mounted the microtubules on topographic surface features generated by UV-nanoimprint lithography...
January 30, 2018: Nano Letters
Edward H Liao, Lindsay Gray, Kazuya Tsurudome, Wassim El Mounzer, Fatima Elazzouzi, Christopher Baim, Sarah Farzin, Mario R Calderon, Grant Kauwe, A Pejmun Haghighi
Retrograde signaling is essential for neuronal growth, function and survival; however, we know little about how signaling endosomes might be directed from synaptic terminals onto retrograde axonal pathways. We have identified Khc-73, a plus-end directed microtubule motor protein, as a regulator of sorting of endosomes in Drosophila larval motor neurons. The number of synaptic boutons and the amount of neurotransmitter release at the Khc-73 mutant larval neuromuscular junction (NMJ) are normal, but we find a significant decrease in the number of presynaptic release sites...
January 26, 2018: PLoS Genetics
Inês Gomes Castro, David Mark Richards, Jeremy Metz, Joseph Liam Costello, Josiah Benjamin Passmore, Tina Angelika Schrader, Ana Gouveia, Daniela Ribeiro, Michael Schrader
Peroxisomes are dynamic organelles which fulfil essential roles in lipid and ROS metabolism. Peroxisome movement and positioning allows interaction with other organelles and is crucial for their cellular function. In mammalian cells, such movement is microtubule-dependent and mediated by kinesin and dynein motors. The mechanisms of motor recruitment to peroxisomes are largely unknown, as well as the role this plays in peroxisome membrane dynamics and proliferation. Here, using a combination of microscopy, live-cell imaging analysis and mathematical modelling, we identify a role for the Ras GTPase MIRO1 as an adaptor for microtubule-dependent peroxisome motility in mammalian cells...
January 24, 2018: Traffic
Michael P N Juniper, Marian Weiss, Ilia Platzman, Joachim P Spatz, Thomas Surrey
Microtubules and motor proteins form active filament networks that are critical for a variety of functions in living cells. Network topology and dynamics are the result of a self-organisation process that takes place within the boundaries of the cell. Previous biochemical in vitro studies with biomimetic systems consisting of purified motors and microtubules have demonstrated that confinement has an important effect on the outcome of the self-organisation process. However, the pathway of motor/microtubule self-organisation under confinement and its effects on network morphology are still poorly understood...
January 24, 2018: Soft Matter
Jing Shen, Jiang-Hui Zhang, Han Xiao, Ji-Min Wu, Kang-Min He, Zhi-Zhen Lv, Zi-Jian Li, Ming Xu, You-Yi Zhang
Membrane nanotubes (MNTs) act as "highways" between cells to facilitate the transfer of multiple signals and play an important role in many diseases. Our previous work reported on the transfer of mitochondria via MNTs between cardiomyocytes (CMs) and cardiac myofibroblasts (MFs); however, the elucidation of the underlying mechanism and pathophysiological significance of this transfer requires additional study. In this study, we determined that the mean movement velocity of mitochondria in MNTs between CMs and MFs was approximately 17...
January 23, 2018: Cell Death & Disease
Zhiyi Lv, Jan Rosenbaum, Timo Aspelmeier, Jörg Großhans
Motor proteins are important for transport and force generation in a variety of cellular processes and morphogenesis. Here we design a general strategy for conditional motor mutants by inserting a protease cleavage site into the "neck" between the head domain and the stalk of the motor protein, making the protein susceptible to proteolytic cleavage at the neck by the corresponding protease. To demonstrate the feasibility of this approach, we inserted the cleavage site of TEV protease into the neck of the tetrameric motor Kinesin-5...
January 3, 2018: Journal of Cell Science
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
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
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
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