Retinoid X receptor in motion: Subtype-specific organization and dynamics of condensate-like assemblies

Biomolecular condensates have emerged as important regulators of gene expression, yet their contribution to nuclear receptor function remains poorly understood. Here, we demonstrate that retinoid X receptors (RXRs) form distinct condensate-like assemblies, the properties of which depend on receptor subtype, ligand binding, and subcellular localization. RXRα, RXRβ, and RXRγ exhibit marked differences in spatial organization and molecular dynamics, indicating subtype-specific modes of higher-order receptor organization. Deletion analyses identify the intrinsically disordered AB region as a determinant of subtype-specific assembly organization and dynamics. In the nucleus, only 9cRA-induced RXRα and RXRγ foci colocalize with transcription initiation-associated RNA polymerase II, whereas fine puncta and RXRβ assemblies show no detectable overlap, highlighting functional heterogeneity within the nuclear RXR population. Beyond the nucleus, RXRα and RXRγ form 9cRA-induced cytoplasmic droplets exhibiting liquid-like behavior, including fusion events and rapid molecular exchange, indicating that higher-order RXR organization is not restricted to the nuclear compartment. Together, our findings uncover subtype-specific and compartment-specific principles governing the organization and dynamics of RXR condensate-like assemblies and suggest that distinct assemblies contribute to compartment-specific RXR functions.