Location-biased β-arrestin conformations direct GPCR signaling Biosensors reveal the effects of β-arrestin conformations on GPCR signaling at different subcellular locations.

Through real-time imaging of live cells, researchers reveal yet another level of complexity in the spatiotemporal regulation of G protein–coupled receptors, the targets of approximately 30% of all FDA-approved drugs.

Learn more in #ScienceSignaling: https://scim.ag/4dKehNL

DDX3X is a Cl−-sensitive RNA helicase A disease-associated mutation blocks Cl− binding from functionally affecting the RNA helicase DDX3X.

A new #ScienceSignaling study demonstrates how chloride ions alter the function of the RNA-unwinding enzyme #DDX3X and reveals how a mutation linked to a severe neurodevelopmental disorder could disrupt the regulation of neurodevelopment by chloride ions. https://scim.ag/4lQE2xP

Contents | Science Signaling 19, 930

Don’t miss this week’s issue of #ScienceSignaling!

A new study shows how chloride ions shape the function of an RNA-unwinding enzyme, real-time cell imaging experiments uncover a new layer of complexity in GPCR signaling, and more.

scim.ag/4rPeAKE

The image shows stress granules formed by DDX3X with a disease-associated mutation that attenuates the inhibitory effects of chloride ions.

Don’t miss this week’s issue of #ScienceSignaling!

A new study shows how chloride ions shape the function of an RNA-unwinding enzyme, real-time cell imaging experiments uncover a new layer of complexity in GPCR signaling, and more. https://scim.ag/40QgdN7

The unphosphorylated, closed form of ezrin binds to RNA to maintain a metastatic phenotype in osteosarcoma cells Unphosphorylated ezrin is not dormant but rather binds to RNAs to regulate transcription and translation.

Researchers in #ScienceSignaling have found that the closed form of the protein ezrin is functional instead of being inactive as previously assumed—and that this form may promote the metastasis of bone cancer cells. https://scim.ag/478qMPi

Redox regulation of the transcription factor HAT1 limits basal defenses and promotes responses to infection in Arabidopsis thaliana The redox status of cysteine residues in a transcription factor balances plant defense gene expression.

A study in #ScienceSignaling reveals a molecular “brake” in plants that fine-tunes the immune response to infection, casting light on the sophisticated and dynamic pathways that enable plants to balance energy between growth and immune defense. https://scim.ag/4btk9bt

Redox regulation of the transcription factor HAT1 limits basal defenses and promotes responses to infection in Arabidopsis thaliana The redox status of cysteine residues in a transcription factor balances plant defense gene expression.

A study in #ScienceSignaling reveals a molecular “brake” in plants that fine-tunes the immune response to infection, casting light on the sophisticated and dynamic pathways that enable plants to balance energy between growth and immune defense.

📄: scim.ag/4sUJu5q

The image shows colocalization of HAT1 and TGA3 (green) in cells of a tobacco leaf. Cell outlines are shown in white, and nuclei are labeled in blue.

This week’s new issue of #ScienceSignaling is here!

Scientists identify a redox switch in plants that fine-tunes the plant immune system’s response to infections, a team discovers metastatic functions for a protein long assumed to be inactive, and more. https://scim.ag/3NhUt9P

Sleep loss is a metabolic disorder Sleep deprivation shifts metabolic resources and deprioritizes processes that support cognition.

In a 2025 #ScienceSignaling Review, researchers discussed an emerging body of research on the metabolic effects of sleep loss, which disrupts the natural balance of energy within neurons.

AI might be the next stage of our natural evolution: A cancer neuroscience perspective Understanding the interactions between cancer and the nervous system may require AI-based analytics.

The emergence of AI tools is not only helpful in cancer #neuroscience, but may be a necessary step to decode the highly complex networks that connect cancer cells to the nervous and immune systems, researchers argue in a new #ScienceSignaling Focus. https://scim.ag/3P61s6j

Human and mouse long noncoding RNAs reengineered for exogenous delivery reduce LPS-induced inflammation in human macrophages and mice Acute inflammation in macrophages and mice can be alleviated by optimized lncRNAs and delivery vehicle.

New work in #ScienceSignaling exploits long noncoding RNAs in the “dark transcriptome” that possess anti-inflammatory properties by reengineering them to dampen acute inflammation in mice—a finding that could open a new field of lncRNA-based therapies.

📄: scim.ag/40o7kKs

Human and mouse long noncoding RNAs reengineered for exogenous delivery reduce LPS-induced inflammation in human macrophages and mice Acute inflammation in macrophages and mice can be alleviated by optimized lncRNAs and delivery vehicle.

New work in #ScienceSignaling exploits long noncoding RNAs in the “dark transcriptome” that possess anti-inflammatory properties by reengineering them to dampen acute inflammation in mice—a finding that could open a new field of lncRNA-based therapies. https://scim.ag/4lm6wiY

Contents | Science Signaling 19, 928

Don’t miss the new issue of #ScienceSignaling!

Scientists exploit the dark transcriptome to generate one of the first potential lncRNA therapies, a Focus discusses how AI is becoming a necessary tool to decode the mysteries of cancer neuroscience, and more.

scim.ag/4bi4snt

The image depicts a liposome containing RNA molecules.

Don’t miss the new issue of #ScienceSignaling!

Scientists exploit the dark transcriptome to generate one of the first potential lncRNA therapies, a Focus discusses how AI is becoming a necessary tool to decode the mysteries of cancer neuroscience, and more. https://scim.ag/4rmyIDy

Microglial reactivity and neuroinflammation-driven changes in motivational behaviors are regulated by Orai1 calcium channels The Ca2+ channel Orai1 in microglia links systemic inflammation to depressive-like behaviors in mice.

How does neuroinflammation trigger depressive-like behaviors?

Researchers in #ScienceSignaling show that Orai1 sustains production of proinflammatory cytokines from microglia and that Orai1-deficient mice display less pronounced depressive-like behaviors.

Learn more: scim.ag/3OdXY1c

Hour-scale single-molecule imaging reveals dynamic assembly of the Wnt co-receptors LRP6 and ROR2 into common signalosomes A method that extends the duration of single-molecule tracking provides insights on Wnt receptor dynamics.

In #ScienceSignaling, a team of scientists devises a method to extend the time that individual molecules can be tracked in a cell, widening the analysis window from several seconds to more than one hour. https://scim.ag/3OGClH4

Microglial reactivity and neuroinflammation-driven changes in motivational behaviors are regulated by Orai1 calcium channels The Ca2+ channel Orai1 in microglia links systemic inflammation to depressive-like behaviors in mice.

How does #neuroinflammation trigger depressive-like behaviors?

Researchers in #ScienceSignaling show that #Orai1 sustains production of proinflammatory cytokines from microglia and that Orai1-deficient mice display less pronounced depressive-like behaviors. https://scim.ag/4rmJSZQ

Glucose metabolism sustains aberrant STAT3 signaling in colorectal cancer through glycosylated local signaling factors Reducing glucose availability may effectively restrict STAT3-driven growth in colorectal tumors.

Researchers have shown how the metabolism of glucose drives colorectal cancer by activating a growth-fueling signaling pathway—and shown that targeting this pathway can shrink tumors in mice.

Learn more in #ScienceSignaling during #ColorectalCancerAwarenessMonth: scim.ag/4rbJAUF

Glucose metabolism sustains aberrant STAT3 signaling in colorectal cancer through glycosylated local signaling factors Reducing glucose availability may effectively restrict STAT3-driven growth in colorectal tumors.

Researchers in #ScienceSignaling have shown how the metabolism of glucose drives #ColorectalCancer by activating a growth-fueling signaling pathway—and shown that targeting this pathway can shrink tumors in mice. https://scim.ag/4aMsGr1 #ColorectalCancerAwarenessMonth

The image shows a colored scanning electron micrograph of part of a human colon cancer cell.

The new issue of #ScienceSignaling has arrived!

A hyperactive signaling pathway presents a new target in colorectal cancer, a new imaging technique extends the tracking of single molecules from seconds to an hour, and more. https://scim.ag/4b17hJg

Temporal proteomic and phosphoproteomic dynamics during neuronal differentiation in the reference iPSC line KOLF2.1J Trace protein and phosphoprotein dynamics during neuronal differentiation in the iPSC-derived cell line model are described.

A new #ScienceSignaling study offers insights into the KOLF2.IJ cell line, which is derived from induced pluripotent stem cells and has been proposed as a neuronal model for Alzheimer’s disease and related #dementia research. https://scim.ag/4aFNY9O

Structure of the photoreceptor synaptic assembly of the extracellular matrix protein pikachurin with the orphan receptor GPR179 The structure of the orphan GPCR GPR179 bound to the extracellular matrix component pikachurin is solved.

What do you get when #NationalProteinDay and #NationalPokémonDay meet? Pikachurin. ⚡

A 2023 #ScienceSignaling study solved the structure of this extracellular protein that plays an essential role in vision.⁠
⁠
Learn more: https://scim.ag/4s82e0N

Acetate enhances long-term memory in female mice by sex-, context-, and brain region–specific epigenetic and transcriptional remodeling The metabolite acetate supports memory recall in female mice.

Scientists show that the metabolite acetate enhances the formation of long-term memories in female mice, revealing a previously unknown sex difference in the epigenetic mechanisms that support memory formation.

Learn more in #ScienceSignaling: scim.ag/4su9uEz

Acetate enhances long-term memory in female mice by sex-, context-, and brain region–specific epigenetic and transcriptional remodeling The metabolite acetate supports memory recall in female mice.

Researchers in #ScienceSignaling show that the metabolite #acetate enhances the formation of long-term memories in female mice, revealing a previously unknown sex difference in the epigenetic mechanisms that support memory formation. https://scim.ag/4cLA6vS

Contents | Science Signaling 19, 926

Scientists discover memory-enhancing properties of acetate unique to female mice, a new Review explores the latest discoveries about metabolic reprogramming after traumatic nerve injury, and more this week in #ScienceSignaling.

scim.ag/40qwjg9

It's been an honor to lead this work & its development from start to end. I extend my deepest appreciation to my co-authors and their invaluable dedication & contributions.
I hope this work is enjoyed by & sparks scientific curiosity for its readers✨ #neuroepigenetics #ScienceSignaling @science.org

The image is a colored transmission electron micrograph of a section through a myelin (red)-ensheathed nerve axon (blue), which is regenerating within a Schwann cell (light brown) located within the basement membrane (pink) of an old Schwann cell.

Scientists discover memory-enhancing properties of acetate unique to female mice, a new Review explores the latest discoveries about metabolic reprogramming after traumatic nerve injury, and more this week in #ScienceSignaling. https://scim.ag/4qWS0PU

Activation of GPR97/ADGRG3 by its tethered agonist, but not by beclomethasone, induces neutrophil polarization and migration The adhesion GPCR GPR97 is most effectively activated by its tethered agonist.

A new in vitro study in #ScienceSignaling demonstrates the mechanism of activation for adhesion G protein-coupled receptors (#AGPCRs), which are found in every organ system and are involved in cell adhesion or cell-cell interactions. https://scim.ag/4rWUMW2

Microglial reactivity and neuroinflammation-driven changes in motivational behaviors are regulated by Orai1 calcium channels The Ca2+ channel Orai1 in microglia links systemic inflammation to depressive-like behaviors in mice.

A calcium channel named Orai1 present in immune cells called #microglia may explain how neuroinflammation can induce depressive-like behaviors, according to new experiments in mice published in #ScienceSignaling. https://scim.ag/4rmJSZQ

The 17 February 2026 cover of Science Signaling. The image shows LPS-induced increases in labeling for a microglial marker (red) or an astrocyte marker (green) in the CA1 region of the hippocampus, effects not seen in mice lacking Orai1 in microglia.

The new issue of #ScienceSignaling has arrived!

Research in mice shows how microglia can trigger depressive-like behaviors linked to neuroinflammation, in vitro work reveals that adhesion GPCRs aren’t activated by corticosteroids, and more. https://scim.ag/3MAVsl5