Beyond the Plasma Membrane: Nuclear G Protein‐Coupled Receptors With a Focus on Angiotensin Receptors

ABSTRACT

G protein‐coupled receptors (GPCRs) have traditionally been described as seven‐transmembrane receptors located at the plasma membrane. However, it is now well established that these receptors can also signal from intracellular membrane compartments, including endosomes, mitochondria, the Golgi apparatus, and nuclear membranes. Importantly, such intracellular signaling can generate distinct functional outcomes even when similar G protein–mediated pathways and second messenger systems are engaged. In this context, increasing evidence indicates that angiotensin receptors, which are GPCRs, are not restricted to the cell surface but can also localize to intracellular compartments, particularly the nucleus. This intracellular distribution supports the concept of an intracrine renin–angiotensin system, in which nuclear angiotensin receptors may directly regulate gene expression and cellular function. Thus, nuclear GPCR signaling represents an additional layer of complexity in angiotensin receptor biology, extending beyond classical membrane‐initiated pathways. This review focuses on nuclear angiotensin receptors, their signaling properties, and their functional relevance in regulating cellular responses.