Biomolecular condensates (BMCs) are non-membranous structures that provide a platform to coordinate the assembly of a specific subset of molecules. BMCs play various roles in cell signal amplification, storage and trafficking of biomolecules. The activator of G-protein signaling 3 (AGS3) appears to have an inherent propensity to form BMCs. However, how the dynamics of AGS3-BMCs are regulated is unclear. In this study (Vural and Lanier, 2024), the authors focus on the dynamics of AGS3-BMCs in response to oxidative, pH and thermal cellular stresses. Notably, AGS3 can also form BMCs with its binding partner dishevelled 2 (DVL2), called AGS3-DVL2-BMCs, an interaction regulated by the signalling protein Gαi3. In response to stress, AGS3 forms BMCs distinct from DVL2 and other types of stress granules. This re-localisation of AGS3 in response to stress is also negatively regulated by Gαi3. Fluorescent recovery after photobleaching (FRAP) of AGS3-BMCs further reveals distinct diffusion kinetics and altered fluidity for AGS3-BMCs when compared to AGS3-DVL2-BMCs, confirming the distinct nature of these particles. Together, this work provides insights into the formation and dynamics of a new subpopulation of condensates, AGS3-BMCs, which serve as a new signal-processing node in response to environmental stress.
