Dynamic Response Diversity of NFAT Isoforms in Individual Living Cells

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Highlights? Two isoforms of the NFAT proteins possess distinct and diverse dynamic responses ? NFAT4 shows fast, stochastic, and frequency-modulated bursts of nuclear localization ? NFAT1 shows a slow, continuous, and amplitude-modulated nuclear localization ? Dynamic diversity can endow cells with enhanced signal processing capabilities     

Axon Regrowth during Development and Regeneration Following Injury Share Molecular Mechanisms

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Highlights? Initial axon outgrowth and regrowth during remodeling are mechanistically distinct ? The nuclear receptor UNF is necessary for axon regrowth but not for initial growth ? TOR is also required for developmental regrowth but not for initial axon outgrowth ? UNF promotes axon regrowth via the TOR pathway and guidance via unknown mechanisms     

ELF4 Regulates GIGANTEA Chromatin Access through Subnuclear Sequestration

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Highlights? GI forms dynamic subnuclear structures ? GI and ELF4 physically interact at nuclear bodies ? ELF4 regulates subnuclear localization of GI ? ELF4 sequesters GI to nuclear bodies from the CO promoter     

β-Catenin-Driven Binary Fate Specification Segregates Germ Layers in Ascidian Embryos

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Highlights? β-catenin nuclear asymmetry after animal-vegetal-oriented cell divisions ? β-catenin nuclear asymmetry drives binary cell fate choices ? Combinatorial codes of nuclear β-catenin activation segregate ascidian germ layers ? Nuclear β-catenin ON-to-OFF activity is required for marginal mesoderm formation     

Metabolic Stress Controls mTORC1 Lysosomal Localization and Dimerization by Regulating the TTT-RUVBL1/2 Complex

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Highlights? Glucose and glutamine feed back to promote mTORC1 signaling through ATP production ? Energetic stress prevents mTOR lysosomal localization independently of AMPK and Rag ? ATP-dependent TTT-RUVBL complex is disassembled and repressed by energetic stress ? TTT-RUVBL is required for mTORC1 functional assembly and lysosomal localization     

A Predictive Computational Model of the Dynamic 3D Interphase Yeast Nucleus

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Highlights? We describe a predictive computational model of dynamic chromosomes in the yeast nucleus ? The model quantitatively recapitulates experimental data on nuclear organization ? The model predicts nuclear reorganization in response to treatment by rapamycin ? Large-scale nuclear organization is dominated by unspecific effects of crowded polymers     

Selective Chemical Crosslinking Reveals a Cep57-Cep63-Cep152 Centrosomal Complex

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Highlights? Selective chemical crosslinking identifies novel protein-protein interactions ? Superresolution microcopy defines the localization of centrosomal proteins ? Cep57, Cep63, and Cep152 form a ring-like centrosomal complex     

The Molecular Basis for Substrate Specificity of the Nuclear NIPP1:PP1 Holoenzyme

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Highlights? The first structure of a nuclear PP1 holoenzyme, NIPP1:PP1 ? The NIPP1 helix defines a unique interaction site on PP1 ? Identification of a common PP1-binding pocket, the ΦΦ motif-binding pocket ? Explains the mechanism of nuclear substrate selection by PP1     

Triacylglycerol Synthesis Enzymes Mediate Lipid Droplet Growth by Relocalizing from the ER to Lipid Droplets

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Highlights? Triacylglyceride (TG) synthesis is coupled with lipid droplet (LD) growth ? Two LD populations exist: growing LDs, containing TG enzymes, and small LDs ? Specific TG synthesis enzymes move from the ER to LDs through membrane bridges ? LD localization of TG enzymes mediates expansion of a subset of LDs     

Protein model discrimination using mutational sensitivity derived from deep sequencing

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Highlights? Individual mutant phenotypes in a saturation library derived via deep sequencing ? Residue depth and active-site residue derivation from mutant phenotypes ? Mutant-phenotype-derived parameters used for protein model discrimination ? Derivation of sequence-structure-function relationships without protein isolation     

The E3 Ligase Parkin Maintains Mitochondrial Integrity by Increasing Linear Ubiquitination of NEMO

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Highlights? The stress-protective prosurvival activity of parkin depends on NEMO ? Parkin binds to LUBAC and increases linear ubiquitination of NEMO ? OPA1 is upregulated via parkin/NEMO/NF-κB for maintaining mitochondrial integrity ? TNF-α signaling via NEMO/NF-κB is impaired in parkin-deficient cells     

Myosin-IXA regulates collective epithelial cell migration by targeting RhoGAP activity to cell-cell junctions

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Highlights? Myosin-IXA, an actin-motor- and RhoGAP-protein, is required for collective migration ? Myosin-IXA is required for radial actin bundle assembly at nascent cell-cell contacts ? The localization of myosin-IXA to actin bundles is dependent on its motor domain ? Myosin-IXA RhoGAP domain locally inhibits Rho stabilizing nascent cell-cell contacts     

A dynamic complex of signaling proteins uses polar localization to regulate cell-fate asymmetry in Caulobacter crescentus

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Highlights? DivL, an unorthodox kinase, promotes activation of the master kinase CckA ? Phosphorylated DivK binds directly to DivL to block the activation of CckA ? Cell cycle and cellular asymmetry are driven by changes in DivK phosphorylation ? Full activation of CckA depends on polar localization with a DivK phosphatase, PleC     

Rspo3 binds syndecan 4 and induces Wnt/PCP signaling via clathrin-mediated endocytosis to promote morphogenesis

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Highlights? Discovery that Rspo3 binds syndecan 4 ? Rspo3/Sdc4 induce Wnt/PCP signaling via clathrin-mediated endocytosis ? Rspo3/PCP signaling is essential for gastrulation and cartilage morphogenesis     

Intestinal Tumorigenesis Initiated by Dedifferentiation and Acquisition of Stem-Cell-like Properties

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Highlights? Epithelial nonstem cells can be reprogrammed into tumor-initiating cells ? Dedifferentiation depends on degree of Wnt signaling ? Wnt signaling is enhanced by NFkB via the coactivator CBP ? Differentiation of stem cells into nonstem cells is bidirectional     

Saturated fatty acid and TLR signaling link β cell dysfunction and islet inflammation

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Highlights? Palmitate induces β cell dysfunction by activating inflammatory processes in islets ? β cells sense palmitate via the TLR4 pathway and recruit M1 macrophages to islets ? M1 macrophages play a pivotal role in palmitate-induced β cell dysfunction ? M1 macrophages and inflammation also play a role in β cell dysfunction in T2D models     

Variation in the Dorsal Gradient Distribution Is a Source for Modified Scaling of Germ Layers in Drosophila

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Highlights? The germ layers of Drosophila species are unequally scaled to size during evolution ? Evolutionary changes in nuclear size and density affect the Dl gradient scaling ? Mesodermal variations rely on Dl distribution instead of regulation of target genes ? Dl gradient distortions allow new positioning of ventral neuroectodermal border     

A Dodecameric CcmK2 Structure Suggests β-Carboxysomal Shell Facets Have a Double-Layered Organization

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Highlights? CcmK2 shows a far stronger self-interaction than do other CcmK paralogs ? CcmK2 forms dodecamers via interactions of the αD helix on the concave face ? Hexagonally tiled CcmK2 sheets can weld via this interaction into a double layer ? FRET data supports a double-layered concave-to-concave model of the shell