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Molecular Biology of the Cell

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https://www.readbyqxmd.com/read/28428259/rabl2-interacts-with-the-ift-b-complex-and-cep19-and-participates-in-ciliary-assembly
#1
Yuya Nishijima, Yohei Hagiya, Tomohiro Kubo, Ryota Takei, Yohei Katoh, Kazuhisa Nakayama
Proteins localized to the basal body and the centrosome play crucial roles in ciliary assembly and functions. Although RABL2 and CEP19 are conserved in ciliated organisms and have been implicated in ciliary/flagellar functions, their roles were poorly understood. We here showed that RABL2 interacts with CEP19 and is recruited to the mother centriole and basal body in a CEP19-dependent manner, and that CEP19 is recruited to the centriole probably via its binding to the centrosomal protein FGFR1OP. Disruption of the RABL2 gene in Chlamydomonas reinhardtii resulted in the non-flagellated phenotype, suggesting a crucial role of RABL2 in ciliary/flagellar assembly...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28428258/deletion-of-inositol-requiring-enzyme-1%C3%AE-in-podocytes-disrupts-glomerular-capillary-integrity-and-autophagy
#2
Daniel Robert Kaufman, Joan Papillon, Louise Larose, Takao Iwawaki, Andrey V Cybulsky
Inositol-requiring enzyme-1α (IRE1α) is an endoplasmic reticulum (ER)-transmembrane endoribonuclease-kinase, which plays an essential function in extraembryonic tissues during normal development, and is activated during ER stress. To address the functional role of IRE1α in glomerular podocytes, we produced podocyte-specific IRE1α deletion mice. In male mice, deletion of IRE1α in podocytes resulted in albuminuria beginning at 5 months of age, and worsening with time. Electron microscopy revealed focal podocyte foot process effacement in 9-month old male IRE1α deletion mice, as well as microvillous transformation of podocyte plasma membranes...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28428257/the-size-speed-force-relationship-governs-migratory-cell-response-to-tumorigenic-factors
#3
Aldo Leal-Egaña, Gaelle Letort, Jean-Louis Martiel, Andreas Christ, Timothée Vignaud, Caroline Roelants, Odile Filhol, Manuel Théry
Tumor development progresses through a complex path of biomechanical changes leading first to cell growth and contraction followed by cell de-adhesion, scattering and invasion. Tumorigenic factors may act specifically on one of these steps or have wider spectrum of actions, leading to a variety of effects and thus sometimes to apparent contradictory outcomes. Here we used micropatterned lines of collagen type-I/fibronectin on deformable surfaces to standardize cell behavior and to measure simultaneously cell size, speed of motion and the magnitude of the associated traction forces at the level of a single cell...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28428256/regulation-of-lung-endothelial-permeability-and-inflammatory-responses-by-prostaglandin-a2-role-of-ep4-receptor
#4
Tomomi Ohmura, Yufeng Tian, Nicolene Sarich, Yunbo Ke, Angelo Meliton, Alok S Shah, Katrin Andreasson, Konstantin G Birukov, Anna A Birukova
A role of prostaglandin A2 (PGA2) in modulation of vascular endothelial function remains unknown. We investigated effects of PGA2 on pulmonary endothelial cell (EC) permeability and inflammatory activation and identified a receptor mediating these effects. PGA2 enhanced the EC barrier and protected against barrier dysfunction caused by vasoactive peptide thrombin and proinflammatory bacterial wall lipopolysacharide (LPS). Receptor screening using pharmacologic and molecular inhibitory approaches identified EP4 as a novel PGA2 receptor...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28428255/nucleosome-nucleosome-interactions-via-histone-tails-and-linker-dna-regulate-nuclear-rigidity
#5
Yuta Shimamoto, Sachiko Tamura, Hiroshi Masumoto, Kazuhiro Maeshima
Cells, as well as the nuclei inside them, experience significant mechanical stress in diverse biological processes including contraction, migration, and adhesion. The structural stability of nuclei must therefore be maintained in order to protect genome integrity. Despite extensive knowledge on nuclear architecture and components, however, the underlying physical and molecular mechanisms remain largely unknown. We addressed this in the present study by subjecting isolated human cell nuclei to microneedle-based quantitative micromanipulation with a series of biochemical perturbations of the chromatin...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28428254/a-novel-physiological-role-for-arf1-in-the-formation-of-bi-directional-tubules-from-the-golgi
#6
Francesca Bottanelli, Nicole Kilian, Andreas M Ernst, Felix Rivera-Molina, Lena K Schroeder, Emil B Kromann, Mark D Lessard, Roman S Erdmann, Alanna Schepartz, David Baddeley, Joerg Bewersdorf, Derek Toomre, James E Rothman
Capitalizing on CRISPR/Cas9 gene editing techniques and super-resolution nanoscopy, we have explored the role of the small GTPase ARF1 in mediating transport steps at the Golgi. Surprisingly, beside its well-established role in generating COPI vesicles, we find that ARF1 is additionally involved in the formation of long (∼ 3 μm), thin (∼ 110 nm diameter) tubular carriers. The anterograde and retrograde tubular carriers are both largely free of the classical Golgi coat proteins Coatomer (COPI) and Clathrin...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28428253/twitchin-kinase-inhibits-muscle-activity
#7
Yohei Matsunaga, Hyundoo Hwang, Barbara Franke, Rhys Williams, McKenna Penley, Hiroshi Qadota, Hong Yi, Levi T Morran, Hang Lu, Olga Mayans, Guy M Benian
Muscle sarcomeres contain giant polypeptides composed of multiple immunoglobulin and fibronectin domains and one or two protein kinase domains. Although binding partners for a number of this family's kinase domains have been identified, the catalytic necessity of these kinase domains remains unknown. In addition, various members of this kinase family are suspected pseudokinases with no, or little, activity. Here, we address catalytic necessity for the first time using the prototypic invertebrate representative twitchin (UNC-22) from C...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28404752/scaling-of-cytoskeletal-organization-with-cell-size-in-drosophila
#8
Alison K Spencer, Andrew J Schaumberg, Jennifer A Zallen
Spatially organized macromolecular complexes are essential for cell and tissue function, but the mechanisms that organize micron-scale structures within cells are not well understood. Microtubule-based structures such as mitotic spindles scale with cell size, but less is known about the scaling of actin structures within cells. Actin-rich denticle precursors cover the ventral surface of the Drosophila embryo and larva and provide templates for cuticular structures involved in larval locomotion. Using quantitative imaging and statistical modeling, we demonstrate that denticle number and spacing scale with cell size over a wide range of cell lengths in embryos and larvae...
April 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28404751/chromosomal-passenger-complex-hydrodynamics-suggests-chaperoning-of-the-inactive-state-by-nucleoplasmin-nucleophosmin
#9
Mariah L Hanley, Tae Yeon Yoo, Matthew Sonnett, Daniel J Needleman, Timothy J Mitchison
The chromosomal passenger complex (CPC) is a conserved, essential regulator of cell division. As such, significant anti-cancer drug development efforts have been focused on targeting it, most notably by inhibiting its AURKB kinase subunit. The CPC is activated by AURKB-catalyzed autophosphorylation on multiple subunits, but how this regulates CPC interactions with other mitotic proteins remains unclear. We investigated the hydrodynamic behavior of the CPC in Xenopus laevis egg cytosol using sucrose gradient sedimentation and in HeLa cells using fluorescence correlation spectroscopy (FCS)...
April 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28404750/human-adenine-nucleotide-translocases-physically-and-functionally-interact-with-respirasomes
#10
Ya-Wen Lu, Michelle Grace Acoba, Kandasamy Selvaraju, Tai-Chung Huang, Raja S Nirujogi, Gajanan Sathe, Akhilesh Pandey, Steven M Claypool
Members of the adenine nucleotide translocase (ANT) family exchange ADP for ATP across the mitochondrial inner membrane, an activity that is essential for oxidative phosphorylation (OXPHOS). Mutations in or dysregulation of ANTs is associated with progressive external ophthalmoplegia, cardiomyopathy, non-syndromic intellectual disability, apoptosis and the Warburg effect. Binding partners of human ANTs have not been systematically identified. The absence of such information has prevented a detailed molecular understanding of the assorted ANT-associated diseases including insight into their disparate phenotypic manifestations...
April 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28404749/diffusion-of-lipids-and-gpi-anchored-proteins-in-actin-free-plasma-membrane-vesicles-measured-by-sted-fcs
#11
Falk Schneider, Dominic Waithe, Mathias P Clausen, Silvia Galiani, Thomas Koller, Gunes Ozhan, Christian Eggeling, Erdinc Sezgin
Diffusion and interaction dynamics of molecules at the plasma membrane play an important role in cellular signalling, and they are suggested to be strongly associated with the actin cytoskeleton. Here, we utilise super-resolution STED microscopy combined with fluorescence correlation spectroscopy (STED-FCS) to access and compare the diffusion characteristics of fluorescent lipid analogues and GPI-anchored proteins (GPI-APs) in the live cell plasma membrane and in actin cytoskeleton-free cell-derived giant plasma membrane vesicles (GPMVs)...
April 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28404748/components-of-rna-granules-affect-their-localization-and-dynamics-in-neuronal-dendrites
#12
Kazuhiko Mitsumori, Yosuke Takei, Nobutaka Hirokawa
In neurons, RNA transport is important for local protein synthesis. Messenger RNAs (mRNAs) are transported along dendrites as large RNA granules. The localization and dynamics of Puralpha and Stau1, major components of RNA transport granules, were investigated in cultured hippocampal neurons. Puralpha-positive granules were localized in both the shafts and spines of dendrites. In contrast, Stau1-positive granules tended to be localized mainly in dendritic shafts. More than 90% of Puralpha-positive granules were positive for Stau1 in immature dendrites, while only half were positive in mature dendrites...
April 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28404747/aep3p-dependent-translation-of-yeast-mitochondrial-atp8
#13
Mario H Barros, Alexander Tzagoloff
Translation of mitochondrial gene products in Saccharomyces cerevisiae depends on mRNA-specific activators that bind to the 5' untranslated regions and promote translation on mitochondrial ribosome. Here we demonstrated that Aep3p, previously shown to stabilize the bicistronic ATP8-ATP6 mRNA and to facilitate initiation of translation from unformylated methionine also activates specifically translation of ATP8 This is supported by several lines of evidence. Temperature-sensitive aep3 mutants are selectively blocked in incorporating (35)S-methionine into Atp8p at non-permissive but not at the permissive temperature...
April 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28404746/wound-induced-ca-2-wave-propagates-through-a-simple-release-and-diffusion-mechanism
#14
L Naomi Handly, Roy Wollman
Damage associated molecular patterns (DAMPs) are critical mediators of information concerning tissue damage from damaged cells to neighboring healthy cells. Adenosine triphosphate (ATP) acts as an effective DAMP when released into extracellular space from damaged cells. Extracellular ATP receptors monitor tissue damage and activate a Ca(2+) wave in the surrounding healthy cells. How the Ca(2+) wave propagates through cells following a wound is unclear. Ca(2+) wave activation can occur extracellularly via external receptors or intracellularly through GAP junctions...
April 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28404745/quantitative-high-content-imaging-identifies-novel-regulators-of-neo1-trafficking-at-endosomes
#15
Lauren E Dalton, Björn D M Bean, Michael Davey, Elizabeth Conibear
P4-ATPases are a family of putative phospholipid flippases that regulate lipid membrane asymmetry, which is important for vesicle formation. Two yeast flippases, Drs2 and Neo1, have non-redundant functions in the recycling of the synaptobrevin-like v-SNARE, Snc1, from early endosomes. Drs2 activity is needed to form vesicles and to regulate its own trafficking, suggesting that flippase activity and localization are linked. However, the role of Neo1 in endosomal recycling is not well characterized. To identify novel regulators of Neo1 trafficking and activity at endosomes, we first identified mutants with impaired recycling of a Snc1-based reporter and subsequently used high-content microscopy to classify these mutants based on the localization of Neo1 or its binding partners Mon2 and Dop1...
April 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28381427/the-endoplasmic-reticulum-is-partitioned-asymmetrically-during-mitosis-prior-to-cell-fate-selection-in-proneuronal-cells-in-the-early-drosophila-embryo
#16
Anthony S Eritano, Arturo Altamirano, Sarah Beyeler, Norma Gaytan, Mark Velasquez, Blake Riggs
Asymmetric cell division is the primary mechanism to generate cellular diversity and relies on the correct partitioning of cell fate determinants. However, the mechanism by which these determinants are delivered and positioned is poorly understood and the upstream signal to initiate asymmetric cell division is currently unknown. Here we report that the Endoplasmic Reticulum (ER) is asymmetrically partitioned during mitosis in epithelial cells just prior to delamination and selection of a proneural cell fate in the early Drosophila embryo...
April 5, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28381426/stimulation-of-microtubule-based-transport-by-nucleation-of-microtubules-on-pigment-granules
#17
Irina Semenova, Dipika Gupta, Takeo Usui, Ichiro Hayakawa, Ann Cowan, Vladimir Rodionov
Microtubule (MT)-based transport can be regulated through changes in organization of MT transport tracks, but the mechanisms that regulate these changes are poorly understood. In Xenopus melanophores, aggregation of pigment granules in the cell center involves their capture by the tips of MTs growing toward the cell periphery, and granule aggregation signals facilitate capture by increasing the number of growing MT tips. This increase could be explained by stimulation of MT nucleation either on the centrosome or on the aggregate of pigment granules that gradually forms in the cell center...
April 5, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28381425/an-endosomal-syntaxin-and-the-ap-3-complex-are-required-for-formation-and-maturation-of-candidate-lysosome-related-secretory-organelles-mucocysts-in-tetrahymena-thermophila
#18
Harsimran Kaur, Daniela Sparvoli, Hiroko Osakada, Masaaki Iwamoto, Tokuko Haraguchi, Aaron P Turkewitz
The ciliate Tetrahymena thermophila synthesizes large secretory vesicles called mucocysts. Mucocyst biosynthesis shares features with dense core granules (DCGs) in animal cells, including proteolytic processing of cargo proteins during maturation. However, other molecular features have suggested relatedness to lysosome-related organelles (LROs). LROs, which include diverse organelles in animals, are formed via convergence of secretory and endocytic trafficking. Here we analyzed Tetrahymena Stx7l1p (syntaxin 7-like 1), a Qa SNARE whose homologs in other lineages are linked with vacuoles/LROs...
April 5, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28381424/gsk-3-mediated-phosphorylation-couples-er-golgi-transport-and-nuclear-stabilisation-of-the-creb-h-transcription-factor-to-mediate-apolipoprotein-secretion
#19
Sónia Barbosa, Suzanne Carreira, Peter O'Hare
CREB-H, an ER-anchored transcription factor plays a key role in regulating secretion in metabolic pathways, particularly triglyceride homeostasis. It controls the production both of secretory pathway components and cargoes including apolipoproteins ApoA-IV and ApoC-II, contributing to VLDL/HDL distribution and lipolysis. The key mechanism controlling CREB-H activity involves its ER retention and forward transport to the Golgi, where it is cleaved by Golgi-resident proteases releasing the N-terminal product which traffics to the nucleus to effect transcriptional responses...
April 5, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28381423/integrin-mediated-traction-force-enhances-paxillin-molecular-associations-and-adhesion-dynamics-that-increase-the-invasiveness-of-tumor-cells-into-a-three-dimensional-extracellular-matrix
#20
Armen H Mekhdjian, FuiBoon Kai, Matthew G Rubashkin, Louis S Prahl, Laralynne M Przybyla, Alexandra L McGregor, Emily S Bell, J Matthew Barnes, Christopher C DuFort, Guanqing Ou, Alice C Chang, Luke Cassereau, Steven J Tan, Michael W Pickup, Jonathan N Lakins, Xin Ye, Michael W Davidson, Jan Lammerding, David J Odde, Alexander R Dunn, Valerie M Weaver
Metastasis requires tumor cells to navigate through a stiff stroma, and to squeeze through confined microenvironments. Whether tumors exploit unique biophysical properties to metastasize remains unclear. Data showed that invading mammary tumor cells, when cultured in a stiffened three-dimensional extracellular matrix that recapitulates the primary tumor stroma, adopt a basal-like phenotype. Metastatic tumor cells and basal-like tumor cells exerted higher integrin-mediated traction forces at the bulk and molecular levels, consistent with a motor-clutch model where motors and clutches are both increased...
April 5, 2017: Molecular Biology of the Cell
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