Direct and Indirect Gene Regulation by a Life-Extending FOXO Protein in C. elegans: Roles for GATA Factors and Lipid Gene Regulators

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Highlights? DAF-16 regulates genes both cell autonomously and cell nonautonomously ? DAF-16 can act at in the endoderm to delay muscle aging ? DAF-16 can act at a distance to protect animals from amyloid paralysis ? Cell-non-autonomous gene regulation by DAF-16 involves the lipid-gene regulator MDT-15     

Redox-Dependent Control of FOXO/DAF-16 by Transportin-1

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Highlights? FOXO forms redox-sensitive, disulfide-dependent complexes with several proteins ? Transportin-1 binds to FOXO via a disulfide and regulates its nuclear localization ? Redox and insulin signaling govern FOXO nuclear localization via distinct pathways ? Redox control of longevity protein FOXO/DAF-16 is evolutionarily conserved     

HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity

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Highlights? C. elegans DAF-2 insulin-like signaling negatively regulates HSF-1 activity ? DDL-1 and DDL-2 are negative regulators of HSF-1 ? Formation of a complex containing DDL-1/2 and HSF-1 inhibits HSF-1 activity ? DAF-2 signaling promotes DHIC formation by inhibiting DDL-1 phosphorylation     

Distinct and Overlapping Roles for AP-1 and GGAs Revealed by the “Knocksideways” System

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Highlights? AP-1 knocksideways depletes ～100 proteins from clathrin-coated vesicles (CCVs) ? GGA2 knocksideways mainly depletes hydrolases and their receptors ? GGA2 depends on AP-1 for incorporation into CCVs ? AP-1 acts as a linchpin for intracellular CCV formation and is bidirectional     

Rapid Inactivation of Proteins by Rapamycin-Induced Rerouting to Mitochondria

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Highlights? We have developed a way of getting rid of proteins quickly (i.e., minutes not days) ? This approach provides new insights into the function of the coat protein AP-1     

A Genome-wide RNAi Screen Reveals a Trio-Regulated Rho GTPase Circuitry Transducing Mitogenic Signals Initiated by G Protein-Coupled Receptors

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Highlights? Human cancers harbor frequent mutations in Gq-linked GPCRs and Gα_q subunits ? A genome-wide RNAi screen revealed that Trio is essential for activating AP-1 via Gα_q ? A network of Trio-regulated Rho GTPases and MAPKs links Gq to the nucleus ? A hard-wired Gq-Trio signaling axis promotes the growth of many human malignancies     

The Ciliary G-Protein-Coupled Receptor Gpr161 Negatively Regulates the Sonic Hedgehog Pathway via cAMP Signaling

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Highlights? The GPCR Gpr161 localizes to primary cilia in a Tulp3/IFT-A-dependent manner ? Complete loss of Gpr161 increases Shh signaling in the mouse neural tube ? Gpr161 couples protein kinase A activation to Shh signaling via cAMP signaling ? Shh signaling internalizes Gpr161 from the cilia, preventing its activity     

PPARγ agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein

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Highlights? PPARγ full agonists induce a brown fat phenotype in subcutaneous WAT ? PRDM16 is required for the development of PPARγ agonist-inducible brow adipocytes ? PRDM16 and PPARγ agonists synergistically activate the brown fat gene program ? Browning effect is mediated through the enhanced stability of the PRDM16 protein     

Insights into Negative Regulation by the Glucocorticoid Receptor from Genome-wide Profiling of Inflammatory Cistromes

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Highlights? TLR4 activation dramatically remodels the GR cistrome in macrophages ? Both negative and positive GR enhancers include GREs, NF-κB, and AP-1 sites ? Classical models fail to predict positive or negative polarity of GR regulation ? Hormone treatment marks negative enhancers by histone deacetylation     

Spatial Restriction of FGF Signaling by a Matrix Metalloprotease Controls Branching Morphogenesis

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Highlights? Drosophila Matrix Metalloprotease (Mmp) inhibits FGF signaling ? An FGF – MMP feedback loop regulates branching morphogenesis ? Mmp2 spatially regulates FGF signaling in epithelia     

Quiescent and Active Hippocampal Neural Stem Cells with Distinct Morphologies Respond Selectively to Physiological and Pathological Stimuli and Aging

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Highlights? Notch signaling defines morphologically distinct hippocampal stem cell populations ? Radial and horizontal hippocampal stem cells depend on canonical Notch signaling ? Different neural stem cell subpopulations respond selectively to neurogenic stimuli ? Aging results in a reversible transition of stem cells to a quiescent state     

Dopamine controls neurogenesis in the adult salamander midbrain in homeostasis and during regeneration of dopamine neurons

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Highlights? Regeneration of midbrain dopamine neurons depends on decreased dopamine signaling ? L-dopa inhibits ependymoglia cell proliferation during dopamine neuron regeneration ? Proliferation of ependymoglia cells is constantly suppressed by dopamine signaling ? Inhibition of dopamine signaling evokes neurogenesis by quiescent ependymoglia cells     

Cofactors required for TLR7- and TLR9-dependent innate immune responses

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Highlights? RNAi and systems-based analysis identified 190 TLR7/9 signaling cofactors ? Pathway crossprofiling enabled mapping cofactors to specific NFκB signaling modules ? HRS is a mediator of ubiquitin-dependent nondegradative endosomal TLR sorting     

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     

Trachea-Derived Dpp Controls Adult Midgut Homeostasis in Drosophila

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Highlights? Trachea-derived Dpp/Bmp is required for midgut homeostasis ? Dpp expressed in tracheal cells reach intestinal cells through visceral muscles ? Dpp signaling is activated in enterocytes (ECs) in the Drosophila adult midgut ? Dpp signaling stabilizes ECs to restrict intestinal stem cell proliferation     

Perivascular Nitric Oxide Activates Notch Signaling and Promotes Stem-like Character in PDGF-Induced Glioma Cells

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Highlights? Perivascular niche nitric oxide activates Notch in PDGF-induced gliomas ? Notch signaling drives tumor stem-like characteristics and reduces survival ? Loss of eNOS activity decreases tumor stem-like characteristics ? Suppressing eNOS activity prolongs survival in glioma-bearing mice     

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     

Phage dUTPases Control Transfer of Virulence Genes by a Proto-Oncogenic G Protein-like Mechanism

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Highlights? dUTPases are signaling molecules acting in analogous manner to the G proteins ? Binding to dUTP induces a conformational change in the phage-encoded dUTPases ? The dUTP-bound form of the phage dUTPases induces transfer of virulence genes ? The dUTPase P loop-like motif V is the molecular switch of the signaling mechanism     

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