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Journal of Cell Biology

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https://www.readbyqxmd.com/read/28533284/nesprin-1%C3%AE-2-is-essential-for-mouse-postnatal-viability-and-nuclear-positioning-in-skeletal-muscle
#1
Matthew J Stroud, Wei Feng, Jianlin Zhang, Jennifer Veevers, Xi Fang, Larry Gerace, Ju Chen
The position of the nucleus in a cell is controlled by interactions between the linker of nucleoskeleton and cytoskeleton (LINC) complex and the cytoskeleton. Defects in nuclear positioning and abnormal aggregation of nuclei occur in many muscle diseases and correlate with muscle dysfunction. Nesprin 1, which includes multiple isoforms, is an integral component of the LINC complex, critical for nuclear positioning and anchorage in skeletal muscle, and is thought to provide an essential link between nuclei and actin...
May 22, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28515277/histone-chaperone-hira-regulates-neural-progenitor-cell-proliferation-and-neurogenesis-via-%C3%AE-catenin
#2
Yanxin Li, Jianwei Jiao
Histone cell cycle regulator (HIRA) is a histone chaperone and has been identified as an epigenetic regulator. Subsequent studies have provided evidence that HIRA plays key roles in embryonic development, but its function during early neurogenesis remains unknown. Here, we demonstrate that HIRA is enriched in neural progenitor cells, and HIRA knockdown reduces neural progenitor cell proliferation, increases terminal mitosis and cell cycle exit, and ultimately results in premature neuronal differentiation. Additionally, we demonstrate that HIRA enhances β-catenin expression by recruiting H3K4 trimethyltransferase Setd1A, which increases H3K4me3 levels and heightens the promoter activity of β-catenin...
May 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28515276/assembly-of-the-u5-snrnp-component-prpf8-is-controlled-by-the-hsp90-r2tp-chaperones
#3
Anna Malinová, Zuzana Cvačková, Daniel Matějů, Zuzana Hořejší, Claire Abéza, Franck Vandermoere, Edouard Bertrand, David Staněk, Céline Verheggen
Splicing is catalyzed by the spliceosome, a complex of five major small nuclear ribonucleoprotein particles (snRNPs). The pre-mRNA splicing factor PRPF8 is a crucial component of the U5 snRNP, and together with EFTUD2 and SNRNP200, it forms a central module of the spliceosome. Using quantitative proteomics, we identified assembly intermediates containing PRPF8, EFTUD2, and SNRNP200 in association with the HSP90/R2TP complex, its ZNHIT2 cofactor, and additional proteins. HSP90 and R2TP bind unassembled U5 proteins in the cytoplasm, stabilize them, and promote the formation of the U5 snRNP...
May 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28515275/autophagy-in-the-presynaptic-compartment-in-health-and-disease
#4
REVIEW
Vinoy Vijayan, Patrik Verstreken
Synapses are functionally distinct neuronal compartments that are critical for brain function, with synaptic dysfunction being an early pathological feature in aging and disease. Given the large number of proteins needed for synaptic function, the proliferation of defective proteins and the subsequent loss of protein homeostasis may be a leading cause of synaptic dysfunction. Autophagic mechanisms are cellular digestion processes that recycle cellular components and contribute to protein homeostasis. Autophagy is important within the nervous system, but its function in specific compartments such as the synapse has been unclear...
May 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28512144/tog-tubulin-binding-specificity-promotes-microtubule-dynamics-and-mitotic-spindle-formation
#5
Amy E Byrnes, Kevin C Slep
XMAP215, CLASP, and Crescerin use arrayed tubulin-binding tumor overexpressed gene (TOG) domains to modulate microtubule dynamics. We hypothesized that TOGs have distinct architectures and tubulin-binding properties that underlie each family's ability to promote microtubule polymerization or pause. As a model, we investigated the pentameric TOG array of a Drosophila melanogaster XMAP215 member, Msps. We found that Msps TOGs have distinct architectures that bind either free or polymerized tubulin, and that a polarized array drives microtubule polymerization...
May 16, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28512143/diverse-roles-of-guanine-nucleotide-exchange-factors-in-regulating-collective-cell-migration
#6
Assaf Zaritsky, Yun-Yu Tseng, M Angeles Rabadán, Shefali Krishna, Michael Overholtzer, Gaudenz Danuser, Alan Hall
Efficient collective migration depends on a balance between contractility and cytoskeletal rearrangements, adhesion, and mechanical cell-cell communication, all controlled by GTPases of the RHO family. By comprehensive screening of guanine nucleotide exchange factors (GEFs) in human bronchial epithelial cell monolayers, we identified GEFs that are required for collective migration at large, such as SOS1 and β-PIX, and RHOA GEFs that are implicated in intercellular communication. Down-regulation of the latter GEFs differentially enhanced front-to-back propagation of guidance cues through the monolayer and was mirrored by down-regulation of RHOA expression and myosin II activity...
May 16, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28512142/a-well-known-potassium-channel-plays-a-critical-role-in-lysosomes
#7
Michael X Zhu
Whole-endolysosome patch clamping presents new opportunities to identify and characterize channels pivotal for these acidic organelles. In this issue (Wang et al., 2017. J. Cell Biol. https://doi.org/10.1083/jcb.201612123), the identification of a role for the large conductance calcium-activated potassium channel brings new thinking about regulation of lysosome membrane potential and function.
May 16, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28512141/oncogene-inducible-organoids-as-a-miniature-platform-to-assess-cancer-characteristics
#8
Tomohiro Mizutani, Yoshiyuki Tsukamoto, Hans Clevers
Direct effects of oncogenic proteins or inhibitor treatments on signaling pathways are difficult to assess in transgenic mice. In this issue, Riemer et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201610058) demonstrate that oncogene-inducible organoids offer the experimental versatility of two-dimensional cell lines, while closely representing the in vivo situation.
May 16, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28507004/choosing-the-right-response-to-er-stress
#9
Ben Short
Cells use distinct unfolded protein response transducers to export different collagens during development.
May 15, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28500183/the-chromokinesin-klp3a-and-microtubules-facilitate-acentric-chromosome-segregation
#10
Travis Karg, Mary Williard Elting, Hannah Vicars, Sophie Dumont, William Sullivan
Although poleward segregation of acentric chromosomes is well documented, the underlying mechanisms remain poorly understood. Here, we demonstrate that microtubules play a key role in poleward movement of acentric chromosome fragments generated in Drosophila melanogaster neuroblasts. Acentrics segregate with either telomeres leading or lagging in equal frequency and are preferentially associated with peripheral bundled microtubules. In addition, laser ablation studies demonstrate that segregating acentrics are mechanically associated with microtubules...
May 12, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28500182/upr-transducer-bbf2h7-allows-export-of-type-ii-collagen-in-a-cargo-and-developmental-stage-specific-manner
#11
Tokiro Ishikawa, Takuya Toyama, Yuki Nakamura, Kentaro Tamada, Hitomi Shimizu, Satoshi Ninagawa, Tetsuya Okada, Yasuhiro Kamei, Tomoko Ishikawa-Fujiwara, Takeshi Todo, Eriko Aoyama, Masaharu Takigawa, Akihiro Harada, Kazutoshi Mori
The unfolded protein response (UPR) handles unfolded/misfolded proteins accumulated in the endoplasmic reticulum (ER). However, it is unclear how vertebrates correctly use the total of ten UPR transducers. We have found that ER stress occurs physiologically during early embryonic development in medaka fish and that the smooth alignment of notochord cells requires ATF6 as a UPR transducer, which induces ER chaperones for folding of type VIII (short-chain) collagen. After secretion of hedgehog for tissue patterning, notochord cells differentiate into sheath cells, which synthesize type II collagen...
May 12, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28500181/nucleolar-caspase-2-protecting-us-from-dna-damage
#12
Kenneth J O'Byrne, Derek J Richard
Caspase-2 triggers apoptosis, but how it is activated by different stimuli is unclear. In this issue, Ando et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201608095) delineate two pathways of caspase-2 activation and show that, in response to DNA damage, caspase-2 forms a complex with the PIDDosome and NPM1 within the nucleolus.
May 12, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28495838/usher-syndrome-type-1-associated-cadherins-shape-the-photoreceptor-outer-segment
#13
Cataldo Schietroma, Karine Parain, Amrit Estivalet, Asadollah Aghaie, Jacques Boutet de Monvel, Serge Picaud, José-Alain Sahel, Muriel Perron, Aziz El-Amraoui, Christine Petit
Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but how mutations in USH1 genes lead to retinal dystrophy in patients remains elusive. The USH1 protein complex is associated with calyceal processes, which are microvilli of unknown function surrounding the base of the photoreceptor outer segment. We show that in Xenopus tropicalis, these processes are connected to the outer-segment membrane by links composed of protocadherin-15 (USH1F protein). Protocadherin-15 deficiency, obtained by a knockdown approach, leads to impaired photoreceptor function and abnormally shaped photoreceptor outer segments...
May 11, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28495837/congressing-kinetochores-progressively-load-ska-complexes-to-prevent-force-dependent-detachment
#14
Philip Auckland, Nicholas I Clarke, Stephen J Royle, Andrew D McAinsh
Kinetochores mediate chromosome congression by either sliding along the lattice of spindle microtubules or forming end-on attachments to their depolymerizing plus-ends. By following the fates of individual kinetochores as they congress in live cells, we reveal that the Ska complex is required for a distinct substep of the depolymerization-coupled pulling mechanism. Ska depletion increases the frequency of naturally occurring, force-dependent P kinetochore detachment events, while being dispensable for the initial biorientation and movement of chromosomes...
May 11, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28495836/spatial-regulation-of-organelle-release-from-myosin-v-transport-by-p21-activated-kinases
#15
Richard G Yau, Sara Wong, Lois S Weisman
Correct positioning of organelles is essential to eukaryotic cells. Molecular motors transport organelles to their proper destinations, yet little is known about the pathways that define these destinations. In Saccharomyces cerevisiae, the myosin V motor Myo2 binds the vacuole-specific adapter Vac17 to attach to the vacuole/lysosome and initiate transport. After arrival in the bud, Myo2 releases the vacuole, and Vac17 is degraded. However, the mechanisms that spatially regulate this release were not established...
May 11, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28490474/the-mechanics-of-microtubule-networks-in-cell-division
#16
REVIEW
Scott Forth, Tarun M Kapoor
The primary goal of a dividing somatic cell is to accurately and equally segregate its genome into two new daughter cells. In eukaryotes, this process is performed by a self-organized structure called the mitotic spindle. It has long been appreciated that mechanical forces must be applied to chromosomes. At the same time, the network of microtubules in the spindle must be able to apply and sustain large forces to maintain spindle integrity. Here we consider recent efforts to measure forces generated within microtubule networks by ensembles of key proteins...
May 10, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28483915/rab2-promotes-autophagic-and-endocytic-lysosomal-degradation
#17
Péter Lőrincz, Sarolta Tóth, Péter Benkő, Zsolt Lakatos, Attila Boda, Gábor Glatz, Martina Zobel, Sara Bisi, Krisztina Hegedűs, Szabolcs Takáts, Giorgio Scita, Gábor Juhász
Rab7 promotes fusion of autophagosomes and late endosomes with lysosomes in yeast and metazoan cells, acting together with its effector, the tethering complex HOPS. Here we show that another small GTPase, Rab2, is also required for autophagosome and endosome maturation and proper lysosome function in Drosophila melanogaster We demonstrate that Rab2 binds to HOPS, and that its active, GTP-locked form associates with autolysosomes. Importantly, expression of active Rab2 promotes autolysosomal fusions unlike that of GTP-locked Rab7, suggesting that its amount is normally rate limiting...
May 8, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28473602/wasp-and-scar-are-evolutionarily-conserved-in-actin-filled-pseudopod-based-motility
#18
Lillian K Fritz-Laylin, Samuel J Lord, R Dyche Mullins
Diverse eukaryotic cells crawl through complex environments using distinct modes of migration. To understand the underlying mechanisms and their evolutionary relationships, we must define each mode and identify its phenotypic and molecular markers. In this study, we focus on a widely dispersed migration mode characterized by dynamic actin-filled pseudopods that we call "α-motility." Mining genomic data reveals a clear trend: only organisms with both WASP and SCAR/WAVE-activators of branched actin assembly-make actin-filled pseudopods...
May 4, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28468835/multilevel-regulation-of-an-%C3%AE-arrestin-by-glucose-depletion-controls-hexose-transporter-endocytosis
#19
Junie Hovsepian, Quentin Defenouillère, Véronique Albanèse, Libuše Váchová, Camille Garcia, Zdena Palková, Sébastien Léon
Nutrient availability controls the landscape of nutrient transporters present at the plasma membrane, notably by regulating their ubiquitylation and subsequent endocytosis. In yeast, this involves the Nedd4 ubiquitin ligase Rsp5 and arrestin-related trafficking adaptors (ARTs). ARTs are targeted by signaling pathways and warrant that cargo ubiquitylation and endocytosis appropriately respond to nutritional inputs. Here, we show that glucose deprivation regulates the ART protein Csr2/Art8 at multiple levels to trigger high-affinity glucose transporter endocytosis...
May 3, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28468834/a-voltage-dependent-k-channel-in-the-lysosome-is-required-for-refilling-lysosomal-ca-2-stores
#20
Wuyang Wang, Xiaoli Zhang, Qiong Gao, Maria Lawas, Lu Yu, Xiping Cheng, Mingxue Gu, Nirakar Sahoo, Xinran Li, Ping Li, Stephen Ireland, Andrea Meredith, Haoxing Xu
The resting membrane potential (Δψ) of the cell is negative on the cytosolic side and determined primarily by the plasma membrane's selective permeability to K(+) We show that lysosomal Δψ is set by lysosomal membrane permeabilities to Na(+) and H(+), but not K(+), and is positive on the cytosolic side. An increase in juxta-lysosomal Ca(2+) rapidly reversed lysosomal Δψ by activating a large voltage-dependent and K(+)-selective conductance (LysoKVCa). LysoKVCa is encoded molecularly by SLO1 proteins known for forming plasma membrane BK channels...
May 3, 2017: Journal of Cell Biology
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