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Anuttama Kulkarni, Yasmin Khan, Krishanu Ray
Acetylcholinesterase (AChE), which is implicated in the pathophysiology of neurological disorders, is distributed along the axon and enriched at the presynaptic basal lamina. It hydrolyses the neurotransmitter acetylcholine, which inhibits synaptic transmission. Aberrant AChE activity and ectopic axonal accumulation of the enzyme are associated with neurodegenerative disorders, such as Alzheimer's disease. The molecular mechanism that underlies AChE transport is still unclear. Here, we show that expression of Drosophila AChE tagged with photoactivable green fluorescent protein and m-Cherry (GPAC) in cholinergic neurons compensates for the RNA interference-mediated knockdown of endogenous AChE activity...
December 5, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Ruibai Luo, Pei-Wen Chen, Michael Wagenbach, Xiaoying Jian, Lisa Jenkins, Linda Wordeman, Paul A Randazzo
No abstract text is available yet for this article.
December 2, 2016: Journal of Biological Chemistry
Mehmet Can Uçar, Reinhard Lipowsky
Intracellular transport is performed by molecular motors that pull cargos along cytoskeletal filaments. Many cellular cargos are observed to move bidirectionally, with fast transport in both directions. This behaviour can be understood as a stochastic tug-of-war between two teams of antagonistic motors. The first theoretical model for such a tug-of-war, the Müller-Klumpp-Lipowsky (MKL) model, was based on two simplifying assumptions: (i) both motor teams move with the same velocity in the direction of the stronger team, and (ii) this velocity matching and the associated force balance arise immediately after the rebinding of an unbound motor to the filament...
December 2, 2016: Soft Matter
Si-Kao Guo, Peng-Ye Wang, Ping Xie
Dimeric kinesin can move processively on microtubule filaments by hydrolyzing ATP. Diverse aspects of its movement dynamics have been studied extensively by using various experimental methods. However, the detailed molecular mechanism of the processive movement is still undetermined and a model that can provide a consistent and quantitative explanation of the diverse experimental data is still lacking. Here, we present such a model, with which we study the movement dynamics of the dimer under variations of solution viscosity, external load, ATP concentration, neck linker length, effect of neck linker docking, effect of a large-size particle attached to one kinesin head, etc...
November 27, 2016: Journal of Theoretical Biology
Guoling Tian, Ana G Cristancho, Holly A Dubbs, Grant T Liu, Nicholas J Cowan, Ethan M Goldberg
BACKGROUND: Microtubules are dynamic polymers of α/β tubulin heterodimers that play a critical role in cerebral cortical development, by regulating neuronal migration, differentiation, and morphogenesis. Mutations in genes that encode either α- or β-tubulin or a spectrum of proteins involved in the regulation of microtubule dynamics lead to clinically devastating malformations of cortical development, including lissencephaly. METHODS: This is a single case report or a patient with lissencephaly, developmental delay, nystagmus, persistent hyperplastic primary vitreous, and infantile spasms, and undertook a neurogenetic workup...
November 2016: Molecular Genetics & Genomic Medicine
Cooper A Taylor, Bill R Miller, Soleil S Shah, Carol A Parish
Mutations in the amyloid precursor protein (APP) are responsible for the formation of amyloid-β peptides. These peptides play a role in Alzheimer's and other dementia-related diseases. The cargo binding domain of the kinesin-1 light chain motor protein (KLC1) may be responsible for transporting APP either directly or via interaction with C-jun N-terminal kinase-interacting protein 1 (JIP1). However, to date there has been no direct experimental or computational assessment of such binding at the atomistic level...
November 7, 2016: Proteins
Cuie Chen, Mayu Inaba, Zsolt G Venkei, Yukiko M Yamashita
Asymmetric stem cell division is often accompanied by stereotypical inheritance of the mother and daughter centrosomes. However, it remains unknown whether and how stem cell centrosomes are uniquely regulated and how this regulation may contribute to stem cell fate. Here we identify Klp10A, a microtubule-depolymerizing kinesin of the kinesin-13 family, as the first protein enriched in the stem cell centrosome in Drosophila male germline stem cells (GSCs). Depletion of klp10A results in abnormal elongation of the mother centrosomes in GSCs, suggesting the existence of a stem cell-specific centrosome regulation program...
November 25, 2016: ELife
Georgi Stoychev, Cordula Reuther, Stefan Diez, Leonid Ionov
Biomolecular transport systems based on cytoskeletal filaments and motor proteins have become promising tools for a wide range of nanotechnological applications. In this paper, we report control of such transport systems using substrates with switchable shape. We demonstrate this approach on the example of microtubules gliding on surfaces of self-folding polymer bilayers with adsorbed kinesin motors. The polymer bilayers are able to undergo reversible transitions between flat and tube-like shapes that allow the externally controlled retention and release of gliding microtubules...
November 24, 2016: Angewandte Chemie
Shweta Bendre, Arnaud Rondelet, Conrad Hall, Nadine Schmidt, Yu-Chih Lin, Gary J Brouhard, Alexander W Bird
The dynamic regulation of microtubules (MTs) during mitosis is critical for accurate chromosome segregation and genome stability. Cancer cell lines with hyperstabilized kinetochore MTs have increased segregation errors and elevated chromosomal instability (CIN), but the genetic defects responsible remain largely unknown. The MT depolymerase MCAK (mitotic centromere-associated kinesin) can influence CIN through its impact on MT stability, but how its potent activity is controlled in cells remains unclear. In this study, we show that GTSE1, a protein found overexpressed in aneuploid cancer cell lines and tumors, regulates MT stability during mitosis by inhibiting MCAK MT depolymerase activity...
December 5, 2016: Journal of Cell Biology
Débora M Portilho, Roger Persson, Nathalie Arhel
Viruses are entirely dependent on their ability to infect a host cell in order to replicate. To reach their site of replication as rapidly and efficiently as possible following cell entry, many have evolved elaborate mechanisms to hijack the cellular transport machinery to propel themselves across the cytoplasm. Long-range movements have been shown to involve motor proteins along microtubules (MTs) and direct interactions between viral proteins and dynein and/or kinesin motors have been well described. Although less well-characterized, it is also becoming increasingly clear that non-motile microtubule-associated proteins (MAPs), including structural MAPs of the MAP1 and MAP2 families, and microtubule plus-end tracking proteins (+TIPs), can also promote viral trafficking in infected cells, by mediating interaction of viruses with filaments and/or motor proteins, and modulating filament stability...
November 23, 2016: Biomolecular Concepts
Rui Zhang, Ye Zhou, Mohammad Rahimi, Juan J de Pablo
When a thin film of active, nematic microtubules and kinesin motor clusters is confined on the surface of a vesicle, four +1/2 topological defects oscillate in a periodic manner between tetrahedral and planar arrangements. Here a theoretical description of nematics, coupled to the relevant hydrodynamic equations, is presented here to explain the dynamics of active nematic shells. In extensile microtubule systems, the defects repel each other due to elasticity, and their collective motion leads to closed trajectories along the edges of a cube...
November 21, 2016: Nature Communications
Yafang Liu, Ping Zhan, Zejun Zhou, Ze Xing, Suhua Zhu, Chenhui Ma, Qian Li, Qingqing Zhu, Yingying Miao, Jianya Zhang, Tangfeng Lv, Yong Song
BACKGROUND: The kinesin family member C1 (KIFC1, also known as HSET) is a kinesin superfamily protein (KIFs). Although KIFC1 acts as a crucial role in the development of several human cancers, the KIFC1 expression profile and functional remain unclear in non-small cell lung cancer (NSCLC). METHODS: We collected the fresh NSCLC samples and paired normal lung tissue in patients with lung cancer operation, and detected KIFC1 expression using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blotting...
October 2016: Journal of Thoracic Disease
Kaori H Yamada, Hojin Kang, Asrar B Malik
Vascular endothelial growth factor receptor 2 (VEGFR2) localized on the surface of endothelial cells (ECs) is a key determinant of the magnitude and duration of angiogenesis induced by vascular endothelial growth factor (VEGF). The kinesin family plus-end motor KIF13B transports VEGFR2 to the EC surface, and as such, specific inhibition of polarized VEGFR2 trafficking prevents angiogenesis. We designed a series of bioactive peptides based on deep analysis of VEGFR2-binding domain of KIF13B that compete specifically with VEGFR2 binding of KIF13B and thereby potently inhibit angiogenesis...
November 15, 2016: American Journal of Pathology
Barbara J Mann, Sai K Balchand, Patricia Wadsworth
Mitotic motor proteins generate force to establish and maintain spindle bipolarity but how they are temporally and spatially regulated in vivo is unclear. Prior work demonstrated that the microtubule-associated protein, TPX2, targets Kinesin-5 and Kinesin-12 motors to spindle microtubules. The C-terminal domain of TPX2 regulates the localization and motility of Kinesin-5, Eg5, but if this domain regulates Kinesin-12, Kif15, is not known. We found that the C-terminal domain of TPX2 contributes to the localization of Kif15 to spindle microtubules in cells and suppresses motor walking in vitro Kif15 and Eg5 are partially redundant motors, and overexpressed Kif15 can drive spindle formation in the absence of Eg5 activity...
November 16, 2016: Molecular Biology of the Cell
Carlos M Guardia, Ginny G Farías, Rui Jia, Jing Pu, Juan S Bonifacino
The multiple functions of lysosomes are critically dependent on their ability to undergo bidirectional movement along microtubules between the center and the periphery of the cell. Centrifugal and centripetal movement of lysosomes is mediated by kinesin and dynein motors, respectively. We recently described a multi-subunit complex named BORC that recruits the small GTPase Arl8 to lysosomes to promote their kinesin-dependent movement toward the cell periphery. Here, we show that BORC and Arl8 function upstream of two structurally distinct kinesin types: kinesin-1 (KIF5B) and kinesin-3 (KIF1Bβ and KIF1A)...
November 15, 2016: Cell Reports
Adam G Hendricks, Yale E Goldman
Optical tweezers have been instrumental in uncovering the mechanisms motor proteins use to generate and react to force. While optical traps have primarily been applied to purified, in vitro systems, emerging methods enable measurements in living cells where the actively fluctuating, viscoelastic environment and varying refractive index complicate calibration of the instrument. Here, we describe techniques to calibrate optical traps in living cells using the forced response to sinusoidal oscillations and spontaneous fluctuations, and to measure the forces exerted by endogenous ensembles of kinesin and dynein motor proteins as they transport cargoes in the cell...
2017: Methods in Molecular Biology
Sinan Can, Ahmet Yildiz
Optical tweezers permit measuring motor-filament rupture forces with piconewton sensitivity. For deeper structural and mechanistic understanding of motors, different structural constraints can be induced by pulling motor proteins at various positions and manipulating the direction of the exerted force. Here, we present an optical-trapping approach to investigate the effect of the magnitude and direction of tension applied to the linker element of cytoskeletal motors on motor-filament interactions. Using this approach, force-dependent microtubule release rates of monomeric kinesins can be directly measured by pulling on kinesin's "neck linker" with a constant force...
2017: Methods in Molecular Biology
Jia Duan, Wei Huang, Haiping Shi
Glioma patients have a poor overall survival; however, patients can show distinct clinical outcomes due to the high heterogeneity of the tumor, which may be indicated by certain clinicobiological parameters. Kinesin family member 20A (KIF20A), which participates in cytokinesis and intracellular transportation, has been recently reported to be upregulated in pancreatic cancer, breast cancer, and bladder cancer. In the current study, we investigated the expression of KIF20A in gliomas and its significance in predicting the prognosis after surgery...
2016: OncoTargets and Therapy
Xuan-Mei Piao, Young Joon Byun, Pildu Jeong, Yun-Sok Ha, Eun Sang Yoo, Seok Joong Yun, Wun-Jae Kim
BACKGROUND: KIF11 (kinesin family member 11), a molecular motor protein, is essential to mitosis and cell cycle progression. Inhibitors of KIF11 have been developed as chemotherapeutic agents for the treatment of various cancers. Regarding prostate cancer (PCa), clinical trials using KIF11 inhibitors for the treatment of castration-resistant PCa have been initiated. We hypothesized that a relationship might exist between KIF11 expression and PCa. To investigate the functional activities and clinical usefulness of KIF11 in PCa, we used quantitative real-time reverse transcriptase polymerase chain reaction to monitor the KIF11 expression patterns...
October 19, 2016: Clinical Genitourinary Cancer
Jerónimo Roberto Miranda-Rodríguez, Enrique Salas-Vidal, Hilda Lomelí, Mario Zurita, Denhi Schnabel
Zebrafish germ plasm is composed of mRNAs such as vasa and nanos and of proteins such as Bucky ball, all of which localize symmetrically in four aggregates at the distal region of the first two cleavage furrows. The coordination of actin microfilaments, microtubules and kinesin is essential for the correct localization of the germ plasm. Rho-GTPases, through their effectors, coordinate cytoskeletal dynamics. We address the participation of RhoA and its effector ROCK in germ plasm localization during the transition from two- to eight-cell embryos...
November 9, 2016: Developmental Biology
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