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Kinesin

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https://www.readbyqxmd.com/read/29217769/structural-insights-into-ankyrin-repeat-mediated-recognition-of-the-kinesin-motor-protein-kif21a-by-kank1-a-scaffold-protein-in-focal-adhesion
#1
Wenfei Pan, Kang Sun, Kun Tang, Qingpin Xiao, Chenxue Ma, Cong Yu, Zhiyi Wei
Kidney ankyrin repeat-containing proteins (KANK1/2/3/4) belong to a family of scaffold proteins, playing critical roles in cytoskeleton organization, cell polarity and migration. Mutations in KANK proteins are implicated in cancers and genetic diseases, such as nephrotic syndrome. KANK proteins can bind various target proteins through different protein regions, including a highly conserved ankyrin repeat domain (ANKRD). However, the molecular basis for target recognition by the ANKRD remains elusive. In this study, we solved a high-resolution crystal structure of the ANKRD of KANK1 in complex with a short sequence of the motor protein kinesin family member 21A (KIF21A), revealing that the highly specific target-binding mode of the ANKRD involves combinatorial use of two interfaces...
December 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29211997/challenges-in-estimating-the-motility-parameters-of-single-processive-motor-proteins
#2
Felix Ruhnow, Linda Kloβ, Stefan Diez
Cytoskeletal motor proteins are essential to the function of a wide range of intracellular mechano-systems. The biophysical characterization of their movement along their filamentous tracks is therefore of large importance. Toward this end, single-molecule, in vitro stepping-motility assays are commonly used to determine motor velocity and run length. However, comparing results from such experiments has proved difficult due to influences from variations in the experimental conditions and the data analysis methods...
December 5, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29207133/potential-role-of-microrna%C3%A2-223%C3%A2-3p-in-the-tumorigenesis-of-hepatocellular-carcinoma-a-comprehensive-study-based-on-data-mining-and-bioinformatics
#3
Rui Zhang, Li-Jie Zhang, Mei-Ling Yang, Lan-Shan Huang, Gang Chen, Zhen-Bo Feng
The aims of the present study were to examine the potential role of microRNA‑233‑3p (miR)‑223‑3p in the tumorigenesis of hepatocellular carcinoma (HCC), and to investigate its diagnostic accuracy and potential molecular mechanisms. The expression data of miR‑223‑3p in HCC were obtained from the Gene Expression Omnibus (GEO). Data for the precursor miR‑223 were obtained from The Cancer Genome Atlas (TCGA). The diagnostic role of miR‑223‑3p was identified by the receiver operating curve (ROC), and the diagnostic value of miR‑223‑3p in HCC was calculated from qualified reports in the literature...
November 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29204984/kinesin-kif4a-is-associated-with-chemotherapeutic-drug-resistance-by-regulating-intracellular-trafficking-of-lung-resistance-related-protein
#4
Li-Na Pan, Yuan Zhang, Chang-Jun Zhu, Zhi-Xiong Dong
Multidrug resistance (MDR) is the major impediment to cancer chemotherapy. The expression of lung resistance-related protein (LRP), a non-ATP-binding cassette (ABC) transporter, is high in tumor cells, resulting in their resistance to a variety of cytotoxic drugs. However, the function of LRP in tumor drug resistance is not yet explicit. Our previous studies had shown that Kinesin KIF4A was overexpressed in cisplatin (DDP)-resistant human lung adenocarcinoma cells (A549/DDP cells) compared with A549 cells. The expression of KIF4A in A549 or A549/DDP cells significantly affects cisplatin resistance but the detailed mechanisms remain unclear...
2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/29203870/ift-proteins-spatially-control-the-geometry-of-cleavage-furrow-ingression-and-lumen-positioning
#5
Nicolas Taulet, Benjamin Vitre, Christelle Anguille, Audrey Douanier, Murielle Rocancourt, Michael Taschner, Esben Lorentzen, Arnaud Echard, Benedicte Delaval
Cytokinesis mediates the physical separation of dividing cells and, in 3D epithelia, provides a spatial landmark for lumen formation. Here, we unravel an unexpected role in cytokinesis for proteins of the intraflagellar transport (IFT) machinery, initially characterized for their ciliary role and their link to polycystic kidney disease. Using 2D and 3D cultures of renal cells, we show that IFT proteins are required to correctly shape the central spindle, to control symmetric cleavage furrow ingression and to ensure central lumen positioning...
December 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/29202578/label-free-detection-of-microvesicles-and-proteins-by-the-bundling-of-gliding-microtubules
#6
Samata Chaudhuri, Till Korten, Slobodanka Korten, Gloria Milani, Tobia Lana, Geertruy Te Kronnie, Stefan Diez
Development of miniaturized devices for the rapid and sensitive detection of analyte is crucial for various applications across healthcare, pharmaceutical, environmental, and other industries. Here, we report on the detection of unlabeled analyte by using fluorescently-labeled, antibody-conjugated microtubules in a kinesin-1 gliding motility assay. The detection principle is based on the formation of fluorescent supramolecular assemblies of microtubule bundles and spools in the presence of multivalent analytes...
December 5, 2017: Nano Letters
https://www.readbyqxmd.com/read/29198755/differentiation-between-oppositely-oriented-microtubules-controls-polarized-neuronal-transport
#7
Roderick P Tas, Anaël Chazeau, Bas M C Cloin, Maaike L A Lambers, Casper C Hoogenraad, Lukas C Kapitein
Microtubules are essential for polarized transport in neurons, but how their organization guides motor proteins to axons or dendrites is unclear. Because different motors recognize distinct microtubule properties, we used optical nanoscopy to examine the relationship between microtubule orientations, stability, and modifications. Nanometric tracking of motors to super-resolve microtubules and determine their polarity revealed that in dendrites, stable and acetylated microtubules are mostly oriented minus-end out, while dynamic and tyrosinated microtubules are oriented oppositely...
November 28, 2017: Neuron
https://www.readbyqxmd.com/read/29196473/cell-scientist-to-watch-lukas-kapitein
#8
(no author information available yet)
Lukas Kapitein studied physics at the VU University in Amsterdam and graduated with a master's degree in experimental physics. He went on to do his PhD in the research groups of Christoph Schmidt and Erwin Peterman on the motility of mitotic kinesins, and in 2007, he won the biannual best thesis award from the Dutch society for Biophysics and Biomedical Technology. Lukas then joined the laboratory of Casper Hoogenraad at the Erasmus Medical Center in Rotterdam to work on the cytoskeleton and polarised cargo transport in neurons...
December 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29192291/kif1bp-loss-in-mice-leads-to-defects-in-the-peripheral-and-central-nervous-system-and-perinatal-death
#9
Caroline S Hirst, Lincon A Stamp, Annette J Bergner, Marlene M Hao, Mai X Tran, Jan M Morgan, Matthias Dutschmann, Andrew M Allen, George Paxinos, Teri M Furlong, Sonja J McKeown, Heather M Young
Goldberg-Shprintzen syndrome is a poorly understood condition characterized by learning difficulties, facial dysmorphism, microcephaly, and Hirschsprung disease. GOSHS is due to recessive mutations in KIAA1279, which encodes kinesin family member 1 binding protein (KIF1BP, also known as KBP). We examined the effects of inactivation of Kif1bp in mice. Mice lacking Kif1bp died shortly after birth, and exhibited smaller brains, olfactory bulbs and anterior commissures, and defects in the vagal and sympathetic innervation of the gut...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29190901/kif11-is-required-for-proliferation-and-self-renewal-of-docetaxel-resistant-triple-negative-breast-cancer-cells
#10
Meng Jiang, Huiru Zhuang, Rui Xia, Lei Gan, Yuantao Wu, Junzhe Ma, Yihui Sun, Zhixiang Zhuang
Development of chemoresistance remains a major hurdle for triple negative breast cancer treatment. Previous studies suggest that CD44+/CD24- cells, subpopulation of cancer stem cells with self-renewing and tumor-initiating capacities, are partly responsible for chemoresistance and therapeutic failure of triple negative breast cancer. Therefore, novel agents that target cancer stem cells (CSCs) may improve the clinical outcome. KIF11 (kinesin family member 11), overexpressed in many cancer cells, is a molecular motor protein that plays essential role in mitosis...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29188449/current-and-new-therapeutic-strategies-for-relapsed-and-refractory-multiple-myeloma-an-update
#11
REVIEW
Inger S Nijhof, Niels W C J van de Donk, Sonja Zweegman, Henk M Lokhorst
Although survival of multiple myeloma patients has at least doubled during recent years, most patients eventually relapse, and treatment at this stage may be particularly complex. At the time of relapse, the use of alternative drugs to those given upfront is current practice. However, many new options are currently available for the treatment of relapsed multiple myeloma, including recently approved drugs, such as the second- and third-generation proteasome inhibitors carfilzomib and ixazomib, the immunomodulatory agent pomalidomide, the monoclonal antibodies daratumumab and elotuzumab and the histone deacetylase inhibitor panobinostat, but also new targeted agents are under active investigation (e...
November 29, 2017: Drugs
https://www.readbyqxmd.com/read/29183992/structural-basis-for-the-recognition-of-kinesin-family-member-21a-kif21a-by-the-ankyrin-domains-of-kank1-and-kank2-proteins
#12
Qiong Guo, Shanhui Liao, Zhongliang Zhu, Yue Li, Fudong Li, Chao Xu
A well-controlled microtubule organization is essential for intracellular transport, cytoskeleton maintenance, and cell development. KN motif and ankyrin repeat domain-containing protein 1 (KANK1), a member of KANK family, could recruit kinesin family member 21A (KIF21A) to the cell cortex to control microtubule growth via its C-terminal ankyrin domain. However, how the KANK1 ankyrin domain recognizes KIF21A and whether other KANK proteins can also bind KIF21A remain unknown. Here, using a combination of structural, site-directed mutagenesis, and biochemical studies, we found that a stretch of ~22 amino acids in KIF21A is sufficient for binding to KANK1 and its close homolog KANK2, and solved the complex structure of the KIF21A peptide with either the KANK1 ankyrin domain or the KANK2 ankyrin domain...
November 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29181100/kinesin-family-member-11-contributes-to-the-progression-and-prognosis-of-human-breast-cancer
#13
Yuan-Yuan Pei, Gao-Chi Li, Jian Ran, Feng-Xiang Wei
The present study aimed to clarify the association between kinesin family member 11 (KIF11) and human breast cancer, and the effect of KIF11 on breast cancer cell progression. Western blot analysis, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, retroviral infection, immunohistochemistry staining, MTT assay, anchorage-independent growth ability assay and tumorigenicity assay were all used in the present study. Western blot and RT-qPCR analysis revealed that the expression of KIF11 was markedly increased in malignant cells compared with that in non-tumorous cells at the mRNA and protein level...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29180624/alpha-synuclein-facilitates-to-form-short-unconventional-microtubules-that-have-a-unique-function-in-the-axonal-transport
#14
Shiori Toba, Mingyue Jin, Masami Yamada, Kanako Kumamoto, Sakiko Matsumoto, Takuo Yasunaga, Yuko Fukunaga, Atsuo Miyazawa, Sakiko Fujita, Kyoko Itoh, Shinji Fushiki, Hiroaki Kojima, Hideki Wanibuchi, Yoshiyuki Arai, Takeharu Nagai, Shinji Hirotsune
Although α-synuclein (αSyn) has been linked to Parkinson's disease (PD), the mechanisms underlying the causative role in PD remain unclear. We previously proposed a model for a transportable microtubule (tMT), in which dynein is anchored to a short tMT by LIS1 followed by the kinesin-dependent anterograde transport; however the mechanisms that produce tMTs have not been determined. Our in vitro investigations of microtubule (MT) dynamics revealed that αSyn facilitates the formation of short MTs and preferentially binds to MTs carrying 14 protofilaments (pfs)...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29167382/kinesin-6-kif20b-is-required-for-efficient-cytokinetic-furrowing-and-timely-abscission-in-human-cells
#15
Kerstin M Janisch, Katrina C McNeely, Joseph M Dardick, Samuel H Lim, Noelle D Dwyer
Cytokinesis requires the cooperation of many cytoskeletal and membrane regulators. Most of the major players required for cytokinesis are known, but the temporal regulation and adaptations for different cell types are less understood. KIF20B (previously called MPHOSPH1 or MPP1) is a member of the Kinesin-6 family, which also includes the better-known members KIF23/MKLP1 and KIF20A/MKLP2. Previously, we showed that mouse Kif20b is involved in cerebral cortex growth and midbody organization of neural stem cells...
November 22, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29167352/two-spatially-distinct-kinesin-14-pkl1-and-klp2-generate-collaborative-inward-forces-against-kinesin-5-cut7-in-s-pombe
#16
Masashi Yukawa, Yusuke Yamada, Tomoaki Yamauchi, Takashi Toda
Kinesin motors play central roles in bipolar spindle assembly. In many eukaryotes, spindle pole separation is driven by Kinesin-5 that generates outward force. This outward force is balanced by antagonistic inward force elicited by Kinesin-14 and/or Dynein. In fission yeast, two Kinesin-14s, Pkl1 and Klp2, play an opposing role against Kinesin-5/Cut7. However, how these two Kinesin-14s coordinate individual activities remains elusive. Here we show that while deletion of either pkl1 or klp2 rescues temperature sensitive cut7 mutants, only pkl1 deletion can bypass the lethality caused by cut7 deletion...
November 22, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29163849/the-therapeutic-potential-of-cell-cycle-targeting-in-multiple-myeloma
#17
REVIEW
Anke Maes, Eline Menu, Kim De Veirman, Ken Maes, Karin Vand Erkerken, Elke De Bruyne
Proper cell cycle progression through the interphase and mitosis is regulated by coordinated activation of important cell cycle proteins (including cyclin-dependent kinases and mitotic kinases) and several checkpoint pathways. Aberrant activity of these cell cycle proteins and checkpoint pathways results in deregulation of cell cycle progression, which is one of the key hallmarks of cancer. Consequently, intensive research on targeting these cell cycle regulatory proteins identified several candidate small molecule inhibitors that are able to induce cell cycle arrest and even apoptosis in cancer cells...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29162464/biochemical-and-biophysical-characterization-of-curcumin-binding-to-human-mitotic-kinesin-eg5-iinsights-into-the-inhibitory-mechanism-of-curcumin-on-eg5
#18
Darpan Raghav, Jomon Sebastian, Krishnan Rathinasamy
In this study we have characterized the biochemical and biophysical interactions of curcumin with the mitotic kinesin Eg5 which plays a pivotal role in the separation of centrosomes during cell division. Curcumin bound to the purified Eg5 (Eg5-437H) with a Kd value of 7.8mM. The temperature dependent binding analysis and evaluation of thermodynamic parameters indicated the involvement of static quenching mechanism in the binding process. Evidences from competition experiment with monastrol indicated that curcumin bound to Eg5 at a novel druggable site...
November 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29159770/jip3-localises-to-exocytic-vesicles-and-focal-adhesions-in-the-growth-cones-of-differentiated-pc12-cells
#19
Patrick T Caswell, Martin Dickens
The JNK-interacting protein 3 (JIP3) is a molecular scaffold, expressed predominantly in neurons, that serves to coordinate the activation of the c-Jun N-terminal kinase (JNK) by binding to JNK and the upstream kinases involved in its activation. The JNK pathway is involved in the regulation of many cellular processes including the control of cell survival, cell death and differentiation. JIP3 also associates with microtubule motor proteins such as kinesin and dynein and is likely an adapter protein involved in the tethering of vesicular cargoes to the motors involved in axonal transport in neurons...
November 20, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29158401/kinesin-dependent-mechanism-for-controlling-triglyceride-secretion-from-the-liver
#20
Priyanka Rai, Mukesh Kumar, Geetika Sharma, Pradeep Barak, Saumitra Das, Siddhesh S Kamat, Roop Mallik
Despite massive fluctuations in its internal triglyceride content, the liver secretes triglyceride under tight homeostatic control. This buffering function is most visible after fasting, when liver triglyceride increases manyfold but circulating serum triglyceride barely fluctuates. How the liver controls triglyceride secretion is unknown, but is fundamentally important for lipid and energy homeostasis in animals. Here we find an unexpected cellular and molecular mechanism behind such control. We show that kinesin motors are recruited to triglyceride-rich lipid droplets (LDs) in the liver by the GTPase ARF1, which is a key activator of lipolysis...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
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