Science signaling

01 13 October 2026

DOI 10.1126/scisignal.aem9378

Shutting down GPCRs

Open DOI

John F. Foley

Bifunctional antibodies linking a GPCR with the transferrin receptor lead to GPCR down-regulation.

02 13 October 2026

DOI 10.1126/scisignal.aec5591

Inside-out allosteric regulation of ligand binding and activation of the atypical chemokine receptor ACKR3

Open DOI

Fabian Pfersdorf, Christopher T. Schafer, Tracy M. Handel et al.

Chemokine receptors are G protein–coupled receptors (GPCRs) that drive cell migration through interactions with chemokines. Even in the absence of ligand, chemokine receptors spend a portion of their time in active conformational states,...

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03 13 October 2026

DOI 10.1126/scisignal.aec1743

Clusters of GSDMD and GSDME mediate neutrophil pyroptosis in cryopyrin-associated periodic syndrome

Open DOI

ZheHao Tan, Sahand Salari Namin, Janset Onyuru et al.

The Nod-like receptor family pyrin domain–containing 3 (NLRP3) inflammasome is a cytosolic multiprotein immune sensor that is restrained from assembling at steady state. Mutations in NLRP3 associated with cryopyrin-associated periodic sy...

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04 6 October 2026

DOI 10.1126/scisignal.aed7175

The Gα-interacting protein RGS4 in dorsal root ganglia maintains molecular and behavioral maladaptations in murine pain models

Open DOI

Randal A. Serafini, Bruno Giotti, Alex Luebbers et al.

Regulator of G protein signaling 4 (RGS4) is a Gα subunit–interacting protein that modulates the functional responses of various G protein–coupled receptors (GPCRs) and that is present in several components of the nociceptive circuitry. ...

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05 6 October 2026

DOI 10.1126/scisignal.aeb2392

Metabolic reprogramming of pathogenic CD4 + T helper cells attenuates inflammatory bowel disease in mice

Open DOI

Shravan K. Mishra, Leena M. Abdelrahman, Hyun Se Kim Lee et al.

CD4 + effector T helper 1 (T H 1) cells drive inflammatory bowel disease (IBD). Here, we investigated how integrated signaling, metabolic, and epigenetic programs sustain their pathogenic persistence. We found that enforcing mitochondria...

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06 29 September 2026

DOI 10.1126/scisignal.adw7297

S1P mimics phosphorylation to mediate PDK1-independent activation of aPKC with an opposing downstream effect

Open DOI

Taketoshi Kajimoto, Ambuj Srivastava, Jing Zhang et al.

Atypical protein kinase C (aPKC) isozymes play opposing roles in oncogenic and tumor-suppressive signaling pathways. These kinases are activated by phosphoinositide-dependent kinase 1 (PDK1) as well as by direct binding of the lipid seco...

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07 29 September 2026

DOI 10.1126/scisignal.aei4151

Light-induced remodeling of the Drosophila phosphoproteome regulates visual adaptation through the Trp channel

Open DOI

Lucas D. Kramer, Tal Brandwine-Shemmer, Leah R. Pierce et al.

Light is an important environmental stimulus that is necessary for vision and circadian entrainment. Here, we present a system-wide analysis of the kinase-mediated light response in Drosophila using optimized data-independent acquisition...

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08 22 September 2026

DOI 10.1126/scisignal.aem4471

How some brain macrophages go with the flow

Open DOI

Wei Wong

CMAF drives the identity and signaling of a brain macrophage subset involved in vascular homeostasis.

09 22 September 2026

DOI 10.1126/scisignal.aef0327

PAG supports T cell immune synapse function by binding to actin

Open DOI

Emily K. Moore, Shoiab Bukhari, Justin Zhong et al.

Immunotherapies affect T cell function by modifying the immune synapse, which forms at the interface between T cells and their targets. Phosphoprotein associated with glycosphingolipid-rich microdomains 1 (PAG) is a T cell adaptor protei...

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10 22 September 2026

DOI 10.1126/scisignal.aed1808

Dishevelled drives disassembly of primary cilia through an unusual PDZ domain–mediated binding mode with Girdin-L

Open DOI

Miha Renko, Gonzalo J. Beitia, Trevor J. Rutherford et al.

Dishevelled is a pivotal cytoplasmic hub protein that transmits Wnt signals to various downstream effectors to specify cell fates and behaviors during animal development. The PDZ domain of Dishevelled is dispensable for signaling to β-ca...

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