Protein polymer scaffolds composed of death fold (DF) proteins are critical to the formation of signalosomes in immune signaling. The biophysical properties that these polymeric scaffolds require for ...

A method that extends the duration of single-molecule tracking provides insights on Wnt receptor dynamics.

EGFR hotspot mutations (mEGFR), including primary L858R, exon 19 deletion, and secondary T790M, are pivotal oncogenic drivers in human non-small cell lung cancer (NSCLC). At the same time, NSCLC resis...

A method that extends the duration of single-molecule tracking provides insights on Wnt receptor dynamics.

No description available

Bacterial pathogens rely on their ability to sense and respond to environmental stressors to survive and maintain virulence. The stressosome, a 1.8-megadalton nanomachine, serves as a critical sensor ...

The TIR (Toll/interleukin-1 receptor) domains are found in proteins with roles in the immune systems of humans, plants and bacteria. A combination of structural methods ranging from X-ray and electron crystallography to cryogenic electron microscopy and nuclear magnetic resonance spectroscopy has been required to understand how these domains contribute to signalling, highlighting the complementarity of different structural approaches.

The glucagon-like peptide-1 receptor (GLP-1R) is a class B1 G protein–coupled receptor and major therapeutic target in type 2 diabetes and obesity. Beyond its canonical role in Gαs/cAMP signaling, GLP-1R is increasingly recognized as an organizer of spatiotemporally defined signaling nanodomains, or “signalosomes.” This Review highlights our current knowledge on the mechanisms of assembly and regulation of GLP-1R signalosomes, including the involvement of biomolecular condensates formed by liquid-liquid phase separation, and the role of membrane contact sites between the endoplasmic reticulum (ER) and other organelles as key locations for GLP-1R signaling assemblies. Furthermore, we discuss existing data on the molecular composition and functional impact of two predicted GLP-1R nanodomains, one at ER–plasma membrane contact sites, where GLP-1R might interact with ion channels and transporters to influence local excitability and coordinated insulin secretion, and another at ER–mitochondria membrane contact sites, with the capacity to control lipid and calcium signaling and modulate ER and/or mitochondrial activity. We additionally discuss the role of GLP-1R posttranslational modifications as critical modulators of GLP-1R signal specification and nanodomain organization. Conceptualizing GLP-1R as a dynamic architect of spatiotemporally encoded signalosomes opens new avenues for a deeper understanding of incretin biology with the potential for identification of novel GLP-1R effectors and the development of refined therapeutic strategies for metabolic disease.

A key feature of innate immune signaling is the compartmentalization of signaling effectors into cel