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https://www.readbyqxmd.com/read/29348204/tumor-suppressor-apc-is-an-attenuator-of-spindle-pulling-forces-during-c-elegans-asymmetric-cell-division
#1
Kenji Sugioka, Lars-Eric Fielmich, Kota Mizumoto, Bruce Bowerman, Sander van den Heuvel, Akatsuki Kimura, Hitoshi Sawa
The adenomatous polyposis coli (APC) tumor suppressor has dual functions in Wnt/β-catenin signaling and accurate chromosome segregation and is frequently mutated in colorectal cancers. Although APC contributes to proper cell division, the underlying mechanisms remain poorly understood. Here we show that Caenorhabditis elegans APR-1/APC is an attenuator of the pulling forces acting on the mitotic spindle. During asymmetric cell division of the C. elegans zygote, a LIN-5/NuMA protein complex localizes dynein to the cell cortex to generate pulling forces on astral microtubules that position the mitotic spindle...
January 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29348144/a-crispr-tagging-based-screen-reveals-localized-players-in-wnt-directed-asymmetric-cell-division
#2
Jennifer K Heppert, Ariel M Pani, Allyson M Roberts, Daniel J Dickinson, Bob Goldstein
Oriented cell divisions are critical to establish and maintain cell fates and tissue organization. Diverse extracellular and intracellular cues have been shown to provide spatial information for mitotic spindle positioning, however, the molecular mechanisms by which extracellular signals communicate with cells to direct mitotic spindle positioning are largely unknown. In animal cells, oriented cell divisions are often achieved by the localization of force-generating, motor protein complexes to discrete cortical domains...
January 18, 2018: Genetics
https://www.readbyqxmd.com/read/29335527/myosin-va-is-required-for-preciliary-vesicle-transportation-to-the-mother-centriole-during-ciliogenesis
#3
Chien-Ting Wu, Hsin-Yi Chen, Tang K Tang
Primary cilia play essential roles in signal transduction and development. The docking of preciliary vesicles at the distal appendages of a mother centriole is an initial/critical step of ciliogenesis, but the mechanisms are unclear. Here, we demonstrate that myosin-Va mediates the transportation of preciliary vesicles to the mother centriole and reveal the underlying mechanism. We also show that the myosin-Va-mediated transportation of preciliary vesicles is the earliest event that defines the onset of ciliogenesis...
January 15, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29317490/worm-embryos-need-nude-at-kinetochores-for-dynein-function
#4
(no author information available yet)
No abstract text is available yet for this article.
January 9, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29317443/a-mutation-in-ccdc39-causes-neonatal-hydrocephalus-with-abnormal-motile-cilia-development-in-mice
#5
Zakia Abdelhamed, Shawn M Vuong, Lauren Hill, Crystal Shula, Andrew Timms, David Beier, Kenneth Campbell, Francesco T Mangano, Rolf W Stottmann, June Goto
Pediatric hydrocephalus is characterized by an abnormal accumulation of cerebrospinal fluid (CSF) and is one of the most common congenital brain abnormalities. However, little is known about the molecular and cellular mechanisms regulating CSF flow in the developing brain. Through whole-genome sequencing analysis, we report that a homozygous splice site mutation in coiled-coil domain containing 39 (Ccdc39) is responsible for early postnatal hydrocephalus in the progressive hydrocephalus (prh) mouse mutant. Ccdc39 is selectively expressed in embryonic choroid plexus and ependymal cells on the medial wall of the forebrain ventricle, and the protein is localized to the axoneme of motile cilia...
January 9, 2018: Development
https://www.readbyqxmd.com/read/29316355/finite-element-models-of-flagella-with-sliding-radial-spokes-and-inter-doublet-links-exhibit-propagating-waves-under-steady-dynein-loading
#6
Tianchen Hu, Philip V Bayly
It remains unclear how flagella generate propulsive, oscillatory waveforms. While it is well known that dynein motors, in combination with passive cytoskeletal elements, drive the bending of the axoneme by applying shearing forces and bending moments to microtubule doublets, the origin of rhythmicity is still mysterious. Most conceptual models of flagellar oscillation involve dynein regulation or switching, so that dynein activity first on one side of the axoneme, then the other, drives bending. In contrast, a "viscoelastic flutter" mechanism has recently been proposed, based on a dynamic structural instability...
January 5, 2018: Cytoskeleton
https://www.readbyqxmd.com/read/29311115/miro-proteins-coordinate-microtubule-and-actin-dependent-mitochondrial-transport-and-distribution
#7
Guillermo López-Doménech, Christian Covill-Cooke, Davor Ivankovic, Els F Halff, David F Sheehan, Rosalind Norkett, Nicol Birsa, Josef T Kittler
In the current model of mitochondrial trafficking, Miro1 and Miro2 Rho-GTPases regulate mitochondrial transport along microtubules by linking mitochondria to kinesin and dynein motors. By generating Miro1/2 double-knockout mouse embryos and single- and double-knockout embryonic fibroblasts, we demonstrate the essential and non-redundant roles of Miro proteins for embryonic development and subcellular mitochondrial distribution. Unexpectedly, the TRAK1 and TRAK2 motor protein adaptors can still localise to the outer mitochondrial membrane to drive anterograde mitochondrial motility in Miro1/2 double-knockout cells...
January 8, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29306600/a-missense-mutation-in-dync1h1-gene-causing-spinal-muscular-atrophy-lower-extremity-dominant
#8
Joyutpal Das, James B Lilleker, Kavaldeep Jabbal, John Ealing
Spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder, which causes progressive muscle weakness and in severe cases respiratory failure and death. Although the majority of the SMA cases are autosomal recessive, there is an autosomal dominant variant of SMA that primarily affects the lower extremities, known as 'spinal muscular atrophy - lower extremity, dominant' (SMALED). Mutations in the Dynein Cytoplasmic 1 Heavy Chain 1 (DYNC1H1) gene were the first to be associated with SMALED. Here we report a family with SMALED caused by a pathogenic heterozygous missense c...
December 14, 2017: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/29296987/generic-maps-of-optimality-reveal-two-chemomechanical-coupling-regimes-for-motor-proteins-from-f1-atpase-and-kinesin-to-myosin-and-cytoplasmic-dynein
#9
Zhisong Wang
Many motor proteins achieve high efficiency for chemomechanical conversion, and single-molecule force-resisting experiments are a major tool to detect the chemomechanical coupling of efficient motors. Here, we introduce several quantitative relations that involve only parameters extracted from force-resisting experiments and offer new benchmarks beyond mere efficiency to judge the chemomechanical optimality or deficit of evolutionary remote motors on the same footing. The relations are verified by the experimental data from F1-ATPase, kinesin-1, myosin V and cytoplasmic dynein, which are representative members of four motor protein families...
January 3, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/29276473/ferric-chelate-reductase-1-like-protein-frrs1l-associates-with-dynein-vesicles-and-regulates-glutamatergic-synaptic-transmission
#10
Wenyan Han, Huiqing Wang, Jun Li, Shizhong Zhang, Wei Lu
In the brain, AMPA receptors (AMPARs)-mediated excitatory synaptic transmission is critically regulated by the receptor auxiliary subunits. Recent proteomic studies have identified that Ferric Chelate Reductase 1 Like protein (FRRS1L), whose mutations in human lead to epilepsy, choreoathetosis, and cognitive deficits, is present in native AMPAR complexes in the brain. Here we have characterized FRRS1L in both heterologous cells and in mouse neurons. We found that FRRS1L interacts with both GluA1 and GluA2 subunits of AMPARs, but does not form dimers/oligomers, in HEK cells...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29276125/nek9-phosphorylation-defines-a-new-role-for-tpx2-in-eg5-dependent-centrosome-separation-before-nuclear-envelope-breakdown
#11
Susana Eibes, Núria Gallisà-Suñé, Miquel Rosas-Salvans, Paula Martínez-Delgado, Isabelle Vernos, Joan Roig
Centrosomes [1, 2] play a central role during spindle assembly in most animal cells [3]. In early mitosis, they organize two symmetrical microtubule arrays that upon separation define the two poles of the forming spindle. Centrosome separation is tightly regulated [4, 5], occurring through partially redundant mechanisms that rely on the action of microtubule-based dynein and kinesin motors and the actomyosin system [6]. While centrosomes can separate in prophase or in prometaphase after nuclear envelope breakdown (NEBD), prophase centrosome separation optimizes spindle assembly and minimizes the occurrence of abnormal chromosome attachments that could end in aneuploidy [7, 8]...
December 13, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29274147/doc2b-acts-as-a-calcium-sensor-for-vesicle-priming-requiring-synaptotagmin-1-munc13-2-and-snares
#12
Sébastien Houy, Alexander J Groffen, Iwona Ziomkiewicz, Matthijs Verhage, Paulo S Pinheiro, Jakob Balslev Sørensen
Doc2B is a cytosolic protein with binding sites for Munc13 and Tctex-1 (dynein light chain), and two C2-domains that bind to phospholipids, Ca2+ and SNAREs. Whether Doc2B functions as a calcium sensor akin to synaptotagmins, or in other calcium-independent or calcium-dependent capacities is debated. We here show by mutation and overexpression that Doc2B plays distinct roles in two sequential priming steps in mouse adrenal chromaffin cells. Mutating Ca2+-coordinating aspartates in the C2A-domain localizes Doc2B permanently at the plasma membrane, and renders an upstream priming step Ca2+-independent, whereas a separate function in downstream priming depends on SNARE-binding, Ca2+-binding to the C2B-domain of Doc2B, interaction with ubMunc13-2 and the presence of synaptotagmin-1...
December 23, 2017: ELife
https://www.readbyqxmd.com/read/29273399/behavioral-defects-in-a-dctn1g71a-transgenic-mouse-model-of-perry-syndrome
#13
Takayasu Mishima, Manami Deshimaru, Takuya Watanabe, Kaori Kubota, Mariko Kinoshita-Kawada, Junichi Yuasa-Kawada, Kotaro Takasaki, Yoshinari Uehara, Shozo Jinno, Katsunori Iwasaki, Yoshio Tsuboi
Perry syndrome is a rare neurodegenerative disease characterized by parkinsonism, depression/apathy, weight loss, and central hypoventilation. Our previously-conducted genome-wide association scan and subsequent studies identified nine mutations in DCTN1, the largest protein subunit of the dynactin complex, in patients with Perry syndrome. These included G71A in the microtubule-binding cytoskeleton-associated protein Gly-rich domain of p150Glued. The dynactin complex is essential for function of the microtubule-based cytoplasmic retrograde motor dynein...
December 19, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29247176/she1-affects-dynein-through-direct-interactions-with-the-microtubule-and-the-dynein-microtubule-binding-domain
#14
Kari H Ecklund, Tatsuya Morisaki, Lindsay G Lammers, Matthew G Marzo, Timothy J Stasevich, Steven M Markus
Cytoplasmic dynein is an enormous minus end-directed microtubule motor. Rather than existing as bare tracks, microtubules are bound by numerous microtubule-associated proteins (MAPs) that have the capacity to affect various cellular functions, including motor-mediated transport. One such MAP is She1, a dynein effector that polarizes dynein-mediated spindle movements in budding yeast. Here, we characterize the molecular basis by which She1 affects dynein, providing the first such insight into which a MAP can modulate motor motility...
December 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29241689/nuclear-movement-in-fungi
#15
REVIEW
Xin Xiang
Nuclear movement within a cell occurs in a variety of eukaryotic organisms including yeasts and filamentous fungi. Fungal molecular genetic studies identified the minus-end-directed microtubule motor cytoplasmic dynein as a critical protein for nuclear movement or orientation of the mitotic spindle contained in the nucleus. Studies in the budding yeast first indicated that dynein anchored at the cortex via its anchoring protein Num1 exerts pulling force on an astral microtubule to orient the anaphase spindle across the mother-daughter axis before nuclear division...
December 11, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29240760/novel-linear-motif-filtering-protocol-reveals-the-role-of-the-lc8-dynein-light-chain-in-the-hippo-pathway
#16
Gábor Erdős, Tamás Szaniszló, Mátyás Pajkos, Borbála Hajdu-Soltész, Bence Kiss, Gábor Pál, László Nyitray, Zsuzsanna Dosztányi
Protein-protein interactions (PPIs) formed between short linear motifs and globular domains play important roles in many regulatory and signaling processes but are highly underrepresented in current protein-protein interaction databases. These types of interactions are usually characterized by a specific binding motif that captures the key amino acids shared among the interaction partners. However, the computational proteome-level identification of interaction partners based on the known motif is hindered by the huge number of randomly occurring matches from which biologically relevant motif hits need to be extracted...
December 14, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29235179/snp-g-1007a-g-within-the-porcine-dnal4-gene-affects-sperm-motility-traits-and-percentage-of-midpiece-abnormalities
#17
I Wiedemann, A Maehlmeyer, S Jansen, A R Sharifi, C Knorr
The flagellar beating of a spermatozoa's axoneme is caused by the varying activation and inactivation of dynein molecules. Dynein, axonemal, light chain 4 (DNAL4) is a functional candidate gene for sperm motility as it encodes a small subunit of the dyneins. We resequenced the porcine DNAL4 using three artificial insemination (AI) boars each with high (>68%) or low (<60%) motility, and detected 23 SNP. These were then genotyped for 82 AI boars. Using spermatological records, significantly negative genetic correlations between ejaculate volume (VOL) and the further spermatological parameters concentration (CONC) (r = -...
December 12, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/29235081/overview-of-the-mechanism-of-cytoskeletal-motors-based-on-structure
#18
REVIEW
Yusuke Kato, Takuya Miyakawa, Masaru Tanokura
In the last two decades, a wealth of structural and functional knowledge has been obtained for the three major cytoskeletal motor proteins, myosin, kinesin and dynein, which we review here. The cytoskeletal motor proteins myosin and kinesin are structurally similar in the core architecture of their motor domains and have similar force-producing mechanisms that are coupled with the chemical cycles of ATP binding, hydrolysis, Pi release and subsequent ADP release. The force is generated through conformational changes in the motor domain during Pi release and ATP binding in myosin and kinesin, respectively, and then converted into the rotation of the lever arm or neck linker (referred to as a power stroke) through the common structural pathways...
December 12, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/29232101/a-driver-switchover-mechanism-of-influenza-virus-transport-from-microfilaments-to-microtubules
#19
Li-Juan Zhang, Li Xia, Shu-Lin Liu, En-Ze Sun, Qiu-Mei Wu, Li Wen, Zhi-Ling Zhang, Dai-Wen Pang
When infecting host cells, influenza virus must move on microfilaments (MFs) at the cell periphery and then move along microtubules (MTs) through the cytosol to reach the perinuclear region for genome release. But how viruses switch from the actin roadway to the microtubule highway remains obscure. To settle this issue, we systematically dissected the role of related motor proteins in the transport of influenza virus between cytoskeletal filaments in situ and in real-time using quantum dot (QD)-based single-virus tracking (SVT) and multicolor imaging...
December 12, 2017: ACS Nano
https://www.readbyqxmd.com/read/29228333/dnaaf1-links-heart-laterality-with-the-aaa-atpase-ruvbl1-and-ciliary-intraflagellar-transport
#20
Verity L Hartill, Glenn van de Hoek, Mitali P Patel, Rosie Little, Christopher M Watson, Ian R Berry, Amelia Shoemark, Dina Abdelmottaleb, Emma Parkes, Chiara Bacchelli, Katarzyna Szymanska, Nine V Knoers, Peter J Scambler, Marius Ueffing, Karsten Boldt, Robert Yates, Paul J Winyard, Beryl Adler, Eduardo Moya, Louise Hattingh, Anil Shenoy, Claire Hogg, Eamonn Sheridan, Ronald Roepman, Dominic Norris, Hannah M Mitchison, Rachel H Giles, Colin A Johnson
DNAAF1 (LRRC50) is a cytoplasmic protein required for dynein heavy chain assembly and cilia motility, and DNAAF1 mutations cause primary ciliary dyskinesia (PCD; MIM 613193). We describe four families with DNAAF1 mutations and complex congenital heart disease (CHD). In three families, all affected individuals have typical PCD phenotypes. However, an additional family demonstrates isolated CHD (heterotaxy) in two affected siblings, but no clinical evidence of PCD. We identified a homozygous DNAAF1 missense mutation, p...
December 7, 2017: Human Molecular Genetics
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