Endoplasmic Reticulum Stress and Disease

The cytosolic cysteinyl-tRNA synthetase is capable of regulating ATF4 translation independent of eIF2α phosphorylation state

The paper identifies a novel pathway for ATF4 translation activation through CARS loss, independent of eIF2α phosphorylation and mTOR signaling.

CDNF rescues human iPSCs-derived dopamine neurons through direct binding to unfolded protein response sensors PERK and IRE1α

This study identifies CDNF's mechanism of action by showing it rescues human dopamine neurons through direct binding to UPR sensors PERK and IRE1α.

OST component RPN1 is a novel regulator of IRE1 RNase activity that interacts with multiple distinct IRE1 and PERK complexes

The paper identifies RPN1 as a novel regulator of IRE1 RNase activity through interaction with IRE1 and PERK complexes in Drosophila.

TUDCA modulates drug bioavailability to regulate resistance to acute ER stress in Saccharomyces cerevisiae

This study shows TUDCA reduces drug bioavailability, not directly aiding protein folding, and rescues yeast from ER stress by sequestering toxic compounds.

UPR deficiency in budding yeast reveals a trade-off between ER folding capacity and maintenance of euploidy

This study shows that UPR deficiency in budding yeast leads to aneuploidy, revealing a trade-off between ER folding capacity and euploidy maintenance.

p53 engagement is a hallmark of an unfolded protein response in the nucleus of mammalian cells

The paper shows that unfolded protein in the nucleus activates p53-driven transcription and a cell cycle delay, distinct from cytosolic unfolded protein responses.

Proximity Interactome analyses unveil novel regulators of IRE1a canonical signaling

The paper identifies novel IRE1 interactors that regulate its RNase activity and stability, revealing new functions in the unfolded protein response.

IRE1-dependent GOLIM4 expression controls protein secretion to modulate glioblastoma cell adhesion and migration

This study identifies GOLIM4 as a downstream target of IRE1/XBP1s that regulates protein secretion, affecting glioblastoma cell adhesion and migration.

Differential enrichment of retinal ganglion cells underlies proposed core neurodegenerative transcription programs

The paper reanalyzes core transcription programs in retinal ganglion cell neurodegeneration, revealing that previous findings were due to methodological limitations.

Reprograming gene expression in "hibernating" C. elegans involves the IRE-1/XBP-1 pathway

This study identifies the IRE-1/XBP-1 pathway as critical for cold-induced gene regulation in C. elegans, linking it to survival during cold stress.

DIO-SPOTlight Transgenic Mouse to Functionally Monitor Protein Synthesis Regulated by the Integrated Stress Response

The paper introduces a transgenic mouse line, DIO-SPOTlight, to monitor ISR-regulated protein synthesis in specific cell types across the CNS and other organ systems.

TMX5/TXNDC15, a natural trapping mutant of the PDI family is a client of the proteostatic factor ERp44

The paper identifies TMX5 as a PDI family member that interacts with ERp44 via disulfide bonds, controlling its ER retention and distribution.

The ER stress transcription factor Luman/CREB3 is a novel regulator of Schwann cell survival and myelinating capacity through the activation of the unfolded protein response and cholesterol biosynthesis pathways

This study shows that Luman/CREB3 promotes Schwann cell survival and myelination by activating the UPR and cholesterol biosynthesis pathways.

FicD Sensitizes Cellular Response to Glucose Fluctuations in Mouse Embryonic Fibroblasts

This study investigates the role of FicD in regulating BiP AMPylation and UPR signaling in mouse embryonic fibroblasts under different stress conditions, revealing its impact on stress recovery and protein secretion.

A deep phenotyping study in mouse and iPSC models to understand the role of oligodendroglia in optic neuropathy in Wolfram syndrome

This study investigates the role of oligodendroglia in Wolfram syndrome using mouse models and iPSC-derived cells, finding preserved oligodendroglia function and suggesting alternative targets for treatment.

Reexamining the essentiality of Pdi1 in yeast: A PDI1 knockout is viable in Komagataella phaffii and still produces recombinant disulfide bonded proteins

This study shows that Pdi1 is not essential for viability in Komagataella phaffii and supports proper folding of recombinant proteins despite reduced stress resistance.

Failed Cellular Surveillance Enables Pathogenic Matrix Deposition in a COL2A1-Related Osteoarthritis

The paper develops an iPSC-derived cartilage model to study COL2A1 mutations, revealing that Arg719Cys substitution causes defective collagen-II folding and secretion, leading to matrix dysfunction and osteoarthritis.

Mild hyperthermia-induced thermogenesis in the endoplasmic reticulum defines stress response mechanisms

The paper shows mild hyperthermia induces ER thermogenesis and UPR activation in cells, leading to different stress responses in MEF and U2OS cells.

The UPRER governs the cell-specific response of human dopaminergic neurons to mitochondrial stress

The paper shows that the UPRER coordinates mitochondrial stress responses in human dopaminergic neurons, including mitophagy and lncRNA expression, and identifies a lncRNA involved in translation resumption.

Ethnic variation and structure-function analysis of tauopathy-associated PERK alleles.

The paper analyzes ethnic variation in PERK alleles linked to tauopathies and shows structural and functional impacts of these variants.

ATF4 orchestrates IL-1α-induced senescence in adult neural stem cells

The paper investigates how IL-1 induces senescence in adult neural stem cells via the ATF4 pathway following traumatic brain injury.

Excitotoxic glutamate levels cause the secretion of resident endoplasmic reticulum proteins

The paper shows that glutamate receptor activation causes ER Ca2+ depletion, leading to secretion of ER resident proteins and disrupting proteostasis during excitotoxicity.

Targeting eIF2α in TBI-induced traumatic optic neuropathy: Effects of Salubrinal and the Integrated Stress Response Inhibitor.

This study investigates the effects of Salubrinal and ISRIB on eIF2 phosphorylation in TBI-induced traumatic optic neuropathy, finding that both drugs impair visual function in control animals and show limited benefit in injured mice.

Induction of NASH in the Nwd1-/- mouse liver via SERCA2-dependent endoplasmic reticulum stress

This study shows that Nwd1 knockout mice develop NASH-like liver pathology due to SERCA2 dysfunction and ER stress.

The unfolded protein response of the endoplasmic reticulum protects Caenorhabditis elegans against DNA damage caused by stalled replication forks

This study shows that depletion of DNA primases in C. elegans activates the endoplasmic reticulum unfolded protein response (UPR-ER), which is required to alleviate replication stress.

A WFS1 variant disrupting acceptor splice site uncovers the impact of alternative splicing on β cell apoptosis in a patient with Wolfram syndrome.

This study investigates how a WFS1 splice site mutation affects β cell apoptosis in Wolfram syndrome by analyzing alternative splicing and functional consequences in patient-derived iPSCs.

A Drosophila screen identifies a role for histone methylation in ER stress preconditioning

The paper identifies histone methylation, particularly via the Set1/COMPASS complex, as a key modifier of ER stress preconditioning in Drosophila.

Increased activity of IRE1 improves the clinical presentation of EAE

This study shows that increased IRE1 activity in a mouse model of EAE reduces inflammation and improves motor function, suggesting context-dependent protective effects of ER stress.

Adaptation to ER Stress by Slt2, Counterpart of Human MAP Kinase ERK1/2, via Enhancing Splicing and Translation of HAC1 mRNA in Saccharomyces cerevisiae

This study shows that Slt2 in yeast enhances HAC1 mRNA splicing and translation during ER stress, and human ERK1/2 can substitute for Slt2 in UPR.

DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response

DNL343 reduces neurodegeneration in mouse models by inhibiting the integrated stress response and normalizing dysregulated biomarkers, with potential clinical relevance for vanishing white matter disease.