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Weiwei Luo, Minjun Liao, Yan Liao, Xinhuang Chen, Chunyan Huang, Jiyuan Fan, Weijia Liao
BACKGROUND: KIF18A is associated with a variety of tumours; however, the specific mechanism of action of KIF18A in hepatocellular carcinoma (HCC) remains unclear. In this study, in vitro and in vivo experiments were performed with the aim of exploring the potential function and molecular mechanism of kinesin KIF18A in the occurrence and development of HCC. METHODS: We detected the expression of KIF18A in tumour and adjacent tissues as well as cell proliferation, cell invasion and migration in hepatoma cells after silencing KIF18A...
February 21, 2018: World Journal of Surgical Oncology
P Muthuraja, M Himesh, S Prakash, U Venkatasubramanian, P Manisankar
Kinesin Spindle Protein (KSP) or Eg5 is an essential kinesin that is involved in spindle separation process during mitosis and also unregulated in certain cancer cells. Inhibitors of this enzyme have proved to be effective to block spindle separation followed by mitotic arrest and apoptosis of the cancer cells. Since this enzyme has two allosteric inhibitor binding sites, it's an excellent target for developing drugs for cancer chemotherapy. Many pyrimidine derivatives have been proved to be active against cancer and other enzymes...
February 10, 2018: European Journal of Medicinal Chemistry
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
Susan P Gilbert, Stephanie Guzik-Lendrum, Ivan Rayment
Kinesin-2s are major transporters of cellular cargoes. This subfamily contains both homodimeric kinesins whose catalytic domains result from the same gene product and heterodimeric kinesins with motor domains derived from two different gene products. In this review, we focus on the progress to define the biochemical and biophysical properties of the kinesin-2 family members. Our understanding of their mechanochemical capabilities has been advanced by the ability to identify the kinesin-2 genes in multiple species, expression and purification of these motors for single molecule and ensemble assays, and development of new technologies enabling quantitative measurements of kinesin activity with greater sensitivity...
February 14, 2018: Journal of Biological Chemistry
Yoshiko Matsumoto, Motonobu Saito, Katsuharu Saito, Yasuyuki Kanke, Yohei Watanabe, Hisashi Onozawa, Suguru Hayase, Wataru Sakamoto, Teruhide Ishigame, Tomoyuki Momma, Kensuke Kumamoto, Shinji Ohki, Seiichi Takenoshita
Kinesin family member 4A (KIF4A) is a member of the kinesin 4 subfamily of kinesin-related proteins and serves an important role in cell division. The expression levels of KIF4A have been investigated in numerous types of cancer, including cervical, lung, oral, and breast cancer, and are established to be associated with poor patient prognosis. However, the role of KIF4A, as well as its expression in colorectal cancer (CRC), remains to be elucidated. Therefore, the current study investigated KIF4A expression levels in patients with CRC and demonstrated that its levels were increased in tumor tissues compared with non-tumor tissues...
February 2018: Oncology Letters
Joseph M Muretta, Babu J N Reddy, Guido Scarabelli, Alex F Thompson, Shashank Jariwala, Jennifer Major, Monica Venere, Jeremy N Rich, Belinda Willard, David D Thomas, Jason Stumpff, Barry J Grant, Steven P Gross, Steven S Rosenfeld
Numerous posttranslational modifications have been described in kinesins, but their consequences on motor mechanics are largely unknown. We investigated one of these-acetylation of lysine 146 in Eg5-by creating an acetylation mimetic lysine to glutamine substitution (K146Q). Lysine 146 is located in the α2 helix of the motor domain, where it makes an ionic bond with aspartate 91 on the neighboring α1 helix. Molecular dynamics simulations predict that disrupting this bond enhances catalytic site-neck linker coupling...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Tian Xie, Xingyu Li, Fei Ye, Chenxi Lu, Haitao Huang, Fei Wang, Xiaolei Cao, Chongjun Zhong
The Kinesin family member 2a (KIF2A), that belongs to the Kinesin-13 microtubule depolymerases, plays an important role in cancer cell proliferation, migration and apoptosis in various types of cancer such as gastric cancer, breast cancer, and squamous cell carcinoma of the oral tongue, but, its role and mechanism in lung adenocarcinoma (LUAD) is largely unknown. The present study reported that KIF2A was overexpressed in LUAD tissues as compared with adjacent normal tissues. KIF2A was closely correlated with TNM stage and lymph node metastasis (P < 0...
February 7, 2018: Biochemical and Biophysical Research Communications
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
Qingzhou Feng, Keith J Mickolajczyk, Geng-Yuan Chen, William O Hancock
Kinesin-based cargo transport in cells frequently involves the coordinated activity of multiple motors, including kinesins from different families that move at different speeds. However, compared to the progress at the single-molecule level, mechanisms by which multiple kinesins coordinate their activity during cargo transport are poorly understood. To understand these multimotor coordination mechanisms, defined pairs of kinesin-1 and kinesin-2 motors were assembled on DNA scaffolds and their motility examined in vitro...
January 23, 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
Yanlin Huang, Hongbo Wang, Yifan Lian, Xiaojuan Wu, Liang Zhou, Jialiang Wang, Meihai Deng, Yuehua Huang
Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer-related death worldwide, and the molecular pathogenesis and development of HCC are largely unknown. In the present study, we found that KIF4A expression was upregulated in HCC (678 samples, P = 2.03E-8) based on a meta-analysis of Oncomine database. We further confirmed that both KIF4A mRNA and protein expressions were overexpressed in human HCC tumour tissues as well as cancer cell lines. Higher KIF4A expression was correlated with poorer overall survival (P < 0...
February 2, 2018: Cell Death & Disease
Liuqing Wu, Shengqiang Wang, Yunlin Feng, Weihong Zhao, Wei Zuo, Liang Zhong, Jiamei Lin, Weilu Zhao, Foquan Luo
Preclinical studies suggest that propofol may cause neuronal injury to the developing brain. A previous study demonstrated that, in a rat model, maternal exposure to propofol during early or late pregnancy caused learning and memory impairment in the offspring. However, whether propofol exposure during middle pregnancy can cause long‑term behavioral deficits in the offspring remains to be elucidated. N‑methyl‑D‑aspartate receptor 2B subunit (NR2B) serves a critical role in memory modulation. To exert its function, NR2B must be transported to the neuronal membrane by kinesin family member 17 (KIF17)...
January 24, 2018: Molecular Medicine Reports
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
Jakia Jannat Keya, Ryuhei Suzuki, Arif Md Rashedul Kabir, Daisuke Inoue, Hiroyuki Asanuma, Kazuki Sada, Henry Hess, Akinori Kuzuya, Akira Kakugo
In nature, swarming behavior has evolved repeatedly among motile organisms because it confers a variety of beneficial emergent properties. These include improved information gathering, protection from predators, and resource utilization. Some organisms, e.g., locusts, switch between solitary and swarm behavior in response to external stimuli. Aspects of swarming behavior have been demonstrated for motile supramolecular systems composed of biomolecular motors and cytoskeletal filaments, where cross-linkers induce large scale organization...
January 31, 2018: Nature Communications
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
(no author information available yet)
No abstract text is available yet for this article.
February 1, 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
Ping Xie, Hong Chen
Based on the available experimental evidence, we present a simple and general model to describe the movement dynamics of molecular motors that can move processively on their linear tracks by using the chemical energy derived from ATP hydrolysis. An important aspect of the model is the non-tight coupling between the ATP hydrolysis and mechanical stepping, in contrast to the prevailing models presented in the literature that assume the tight chemomechanical coupling. With kinesin as an example, based on the current model, we study in detail its movement dynamics under a backward load, reproducing well the diverse available single-molecule experimental data such as the forward to backward step ratio, velocity, dwell time, randomness, run length, etc...
January 30, 2018: Physical Chemistry Chemical Physics: PCCP
Muniesh Muthaiyan Shanmugam, Prerana Bhan, Hsin-Yi Huang, Jung Hsieh, Tzu-En Hua, Gong-Her Wu, Helly Punjabi, Víctor Daniel Lee Aplícano, Chih-Wei Chen, Oliver Ingvar Wagner
To understand how ciliopathies such as polycystic kidney disease or Bardet-Biedl syndrome develop, we need to understand the basic molecular mechanisms underlying cilia development. Cilia growth depends on a functional intraflagellar transport (IFT) machinery, and we hypothesized that various kinases and phosphatases might be involved in this regulatory process. A candidate screen revealed two kinases PKG-1 (a cGMP-dependent protein kinase) and GCK-2 (a MAP4K3 kinase involved in mTOR signaling) significantly affecting dye filling, chemotaxis, cilia morphology, and IFT component distribution...
January 29, 2018: Molecular and Cellular Biology
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
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