Neuronal ER Stress Impedes Myeloid-Cell-Induced Vascular Regeneration through IRE1α Degradation of Netrin-1

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Highlights? Canonical ER stress pathways are activated in central neurons during hypoxia/ischemia ? The ER stress endoribonuclease IRE1α degrades the neurovascular guidance cue netrin-1 ? Neuronal-derived netrin-1 activates a reparative proangiogenic program in microglial cells ? Neuronal ER stress prevents reparative angiogenesis in the ischemic neural retina     

Modeling Alzheimer’s Disease with iPSCs Reveals Stress Phenotypes Associated with Intracellular Aβ and Differential Drug Responsiveness

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Highlights? Familial and sporadic Alzheimer’s patient iPSC-derived neural cells were analyzed ? Intracellular Aβ oligomers accumulate in lines from some patients ? Aβ oligomer accumulation is associated with ER and oxidative stress ? DHA-alleviated ER and oxidative stresses improve cell viability     

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     

ER Stress Causes Rapid Loss of Intestinal Epithelial Stemness through Activation of the Unfolded Protein Response

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Highlights? ER stress is induced at the stem cell to TA cell transition in the intestinal epithelium ? ER stress causes loss of stemness in intestinal epithelial stem cells ? Loss of stemness depends on eIF2alpha signaling ? PERK-eIF2alpha signaling is required for normal stem cell differentiation     

Local zones of endoplasmic reticulum complexity confine cargo in neuronal dendrites

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Highlights? The endoplasmic reticulum (ER) in dendrites shows spatial variation in complexity ? Increased complexity occurs at dendritic branch points, confining membrane cargo ? An mGluR/PKC/CLIMP63 pathway bidirectionally regulates ER complexity ? ER complexity controls dendritic morphogenesis and defines sites of branch formation     

Tanycytic VEGF-A Boosts Blood-Hypothalamus Barrier Plasticity and Access of Metabolic Signals to the Arcuate Nucleus in Response to Fasting

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Highlights? Fasting induces the plasticity of brain barriers in hypothalamic feeding regions ? Central neuroglucopenia triggers blood-hypothalamus barrier plasticity ? Fasting-induced brain barrier plasticity requires VEGF-A expression in tanycytes ? The tanycytic barrier modulates blood-borne signals access to CNS feeding circuits     

Cotranslational Response to Proteotoxic Stress by Elongation Pausing of Ribosomes

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Highlights? Proteotoxic stress reduces global protein synthesis by influencing elongation ? Proteotoxic stress induces ribosome pausing on mRNAs in the first 50 codons ? Molecular chaperones facilitate translation elongation by binding to nascent chains ? Ribosomes fine tune elongation rate in response to proteotoxic stress     

Macrophage autophagy plays a protective role in advanced atherosclerosis

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Highlights? Proapoptotic oxidative stress induces autophagy in macrophages (M?s) ? Inhibition of autophagy enhances oxidative stress and apoptosis in M?s ? Atheromata of M?-Atg5^?/?Ldlr^?/? mice have increased apoptosis and plaque necrosis ? Apoptotic Atg5^?/? M?s are poorly recognized by phagocytes in vitro and in atheromata     

Plasma Membrane Tethering of the Cortical ER Necessitates Its Finely Reticulated Architecture

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Highlights? The VAP proteins sustain the ER-plasma membrane attachment in fission yeast ? Footprint of the ER on the cortex is functionally insulated from the cytosol ? Division-site placement requires a patchwork of cortical sites accessible to cytosol     

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     

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     

Structure and 3D Arrangement of Endoplasmic Reticulum Membrane-Associated Ribosomes

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Highlights? Subtomogram average of the canine ER-associated ribosome in situ at 31 Å resolution ? Large subunit rRNA ES27L is in direct contact with the ER membrane ? Sec61, TRAP, and potentially OST and the SP complex are resolved ? ER-associated ribosomes adopt a preferred arrangement, likely polyribosome specific     

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     

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     

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     

Differential Regulation of Distinct Vps34 Complexes by AMPK in Nutrient Stress and Autophagy

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Highlights? Different Vps34 complexes are distinctly regulated upon energy stress ? AMPK activates the proautophagy Vps34 complex by phosphorylating Beclin1 ? AMPK inhibits the nonautophagic Vps34 complex by phosphorylating Vps34 ? ATG14L determines whether the Vps34 complex is activated or inhibited by AMPK     

Endogenous Purification Reveals GREB1 as a Key Estrogen Receptor Regulatory Factor

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Highlights? A proteomic method identifies protein-protein interaction in primary tumors ? GREB1 is the top estrogen-induced ER-interacting protein ? GREB1 is an essential ER cofactor recruited to chromatin ? GREB1 is an independent prognostic marker     

p38 MAPK controls prothrombin expression by regulated RNA 3' end processing

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Highlights? External signals regulate 3′ end mRNA processing through p38 MAPK activation ? The mechanism is controlled by a competitive mRNP formation in the 3′UTR ? The mechanism is activated by acute phase stress and inflammation ? The prototypic thrombin links the mechanism to blood coagulation and tumor spread     

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