Tmem64 Modulates Calcium Signaling during RANKL-Mediated Osteoclast Differentiation

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Highlights? Tmem64-deficient mice show increased bone volume ? Tmem64 deficiency reduces [Ca²⁺]_i oscillation in response to RANKL stimulation ? Tmem64 interacts with SERCA2 ? Tmem64 positively regulates osteoclast formation via SERCA2/Ca²⁺ signaling     

piRNA-Triggered MIWI Ubiquitination and Removal by APC/C in Late Spermatogenesis

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Highlights? MIWI is a substrate of APC/C, and piRNA loading is essential for MIWI ubiquitination ? piRNA loading promotes MIWI binding to the APC/C substrate-binding subunit ? MIWI and piRNAs are coordinately eliminated in late spermatids ? Inhibition of MIWI destruction in late spermatids prevents sperm maturation     

STIM1 Juxtaposes ER to Phagosomes,Generating Ca2+ Hotspots that Boost Phagocytosis

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Highlights? STIM1 drives store-operated recruitment of ER cisternae to phagosomes ? STIM1 is required for Ca²⁺-dependent, high-efficiency phagocytosis ? STIM1 gates phagosomal Ca²⁺ channels, generating periphagosomal Ca²⁺ microdomains     

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     

Characterization and In Vivo Pharmacological Rescue of a Wnt2-Gata6 Pathway Required for Cardiac Inflow Tract Development

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Highlights? Wnt2 is required for atrial and inflow tract morphogenesis ? Wnt2 regulates expansion of secondary heart field progenitors ? Defects in Wnt2^?/? mutants can be rescued using Wnt signaling agonists ? Wnt2 cooperates with Gata6 to regulate cardiac inflow tract development     

ADF/cofilin regulates secretory cargo sorting at the TGN via the Ca2+ ATPase SPCA1

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Highlights? ADF/cofilin localizes to the TGN and binds SPCA1 in an actin-dependent manner ? Dynamic actin regulates the activity of the Ca²⁺ pump SPCA1 ? ADF/cofilin facilitates secretory cargo sorting in a Ca²⁺-dependent manner     

Histone Acetylation Regulates Intracellular pH

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Highlights? Global levels of histone acetylation change in response to pH_i alterations ? Histone deacetylation and acetate transport through H⁺-coupled MCTs regulates pH_i ? Proliferation of T cells results in increases in pH_i and global histone acetylation ? HDAC and MCT inhibitors decrease pH_i     

A master switch couples Mg²⁺-assisted catalysis to domain motion in B. stearothermophilus tryptophanyl-tRNA Synthetase

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Highlights? Combinatorial mutagenesis at four remote sites shifts reaction coordinate stabilities ? Cooperative action of all four sites accounts for the entire catalytic role of Mg2⁺ ? Catalysis of ATP utilization by Mg2⁺ occurs if, and only if, the conformation changes ? This type of allosteric effect may explain vectorial coupling in transducing NTPases     

Conformational dynamics of activation for the pentameric complex of dimeric G protein-coupled receptor and heterotrimeric G protein

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Highlights? Dynamics of dimeric Rho complexes in three different conformational states examined ? Photoactivation of Rho (Rho¹) causes structural relaxation of the helical bundle ? Binding of Gt to Rho¹ reduces flexibility of Rho¹ but increases flexibility in Gt ? Free Rho¹ exhibits different a conformation than it does in the Rho¹-G_t complex     

p58IPK-Mediated Attenuation of the Proapoptotic PERK-CHOP Pathway Allows Malignant Progression upon Low Glucose

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Highlights? Transformation-associated glucose shortage triggers ER stress ? The ER stress acts as barrier to malignancy by triggering UPR-dependent apoptosis ? p58^IPK expression removes the UPR barrier by attenuating its PERK-CHOP branch ? This adaptive mechanism enables implementation of UPR cytoprotective features     

Integration of Chemical and RNAi Multiparametric Profiles Identifies Triggers of Intracellular Mycobacterial Killing

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Highlights? A high-content chemical screen identifies modulators of intracellular mycobacteria ? Three compounds that kill bacteria by altering host processes were validated ? Multiparametric chemical and genetic data sets integrated to identify mode of action ? Modulation of autophagy and endosomal trafficking identified as mode of action     

Bone marrow-derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair

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Highlights? c-kit⁺ cell therapy stimulates endogenous cardiomyocyte progenitors ? Nkx2.5- and Gata4-expressing progenitors increase in the infarct border zone ? c-kit⁺ cell therapy leads to improved cardiac function ? No evidence for cardiomyocyte transdifferentiation by bone marrow progenitors     

SOD1 Integrates Signals from Oxygen and Glucose to Repress Respiration

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Highlights? Glucose and O₂ signal through Cu/Zn SOD1 to repress respiration ? SOD1 binds to and prevents turnover of a casein kinase CK1γ for respiration control ? Superoxide from aerobic glucose metabolism feeds the SOD1 reaction to stabilize CK1γ ? Both human and yeast CK1γ stability are regulated by SOD1     

Cap-assisted internal initiation of translation of histone H4

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Highlights? Two structural elements of histone H4 mRNA drive translation initiation ? Ribosome is tethered by an eIF4E-binding site located in the coding region ? A RNA three-way helix junction element positions ribosome on the start codon ? The m⁷G cap-binding pocket formed by the mRNA controls histone translation     

Structural Basis of Selective Ubiquitination of TRF1 by SCFFbx4

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Highlights? SCF ubiquitin ligase subunit Fbx4 binds TRF1 using an atypical small GTPase fold ? Fbx4 recognizes a globular domain of TRF1, not just short phosphorylated degrons ? Telomere shelterin component TIN2 competes with Fbx4 for TRF1 binding ? TIN2 and SCF^Fbx4 thus control TRF1 ubiquitination and degradation     

Structure of Phosphorylated SF1 Bound to U2AF65 in an Essential Splicing Factor Complex

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Highlights? Splicing factor SF1 phosphorylation on a conserved SPSP motif is required in vivo ? SPSP phosphorylation (P) induces local folding within an SF1/U2AF⁶⁵ interface ? Phosphorylation promotes an acutely bent (P)SF1/U2AF⁶⁵/RNA conformation     

CRL1-FBXO11 Promotes Cdt2 Ubiquitylation and Degradation and Regulates Pr-Set7/Set8-Mediated Cellular Migration

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Highlights? Cullin 4A promotes the autoubiquitylation of Cdt2, a substrate adaptor of CRL4^Cdt2 ? CRL1^FBXO11 also ubiquitylates and promotes the degradation of Cdt2 ? FBXO11 degrades Cdt2 to stabilize Set8 and regulate the response to TGF-β ? FBXO11 is similarly required to stabilize Set8 and promote cell migration     

ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility

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Highlights? ALKBH5 is a mammalian m⁶A RNA demethylase ? RNA demethylation affects mRNA export and RNA metabolism ? RNA demethylation is important for mouse fertility ? Reversible mammalian messenger RNA methylation affects gene expression     

Structural and Functional Analysis of the Regulator of G Protein Signaling 2-Gαq Complex

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Highlights? Two structures of the RGS2-Gα_q complex were determined by X-ray crystallography ? RGS2 binds Gα_q in a manner distinct from how other RGS proteins bind Gα_i/o ? In its distinct pose, RGS2 forms extensive contacts with the α-helical domain of Gα_q ? Helical domain contacts contribute to binding affinity and GAP potency of RGS2     

Identification of Distinct Ligands for the C-type Lectin Receptors Mincle and Dectin-2 in the Pathogenic Fungus Malassezia

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Highlights? Mincle and Dectin-2 cooperatively recognize Malassezia through distinct ligands ? The Mincle ligands in Malassezia are glucosyl- and mannosylglycolipids ? The Dectin-2 ligand in Malassezia is an O-linked mannobiose-rich glycoprotein ? Cytokine response to the respective ligands was impaired in Mincle^?/? and Dectin-2^?/? DCs