Brain Corticosteroid Receptor Dynamics and Trafficking: Implications from Live Cell Imaging

Abstract

Adrenal corticosteroids (cortisol in humans or corticosterone in rodents) exert numerous effects in the central nervous system that regulate the stress response, mood, learning and memory, and various neuroendocrine functions. Corticosterone actions in the brain are mediated by two corticosteroid receptors, glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), and they show a high degree of colocalization in the hippocampal region. These receptors predominantly reside in the cytoplasm without ligand and are translocated into the nucleus upon ligand binding to act as transcriptional factors. Thus, their subcellualr localizations are an important component of their biological activity. Given the differential action of MR and GR in the central nervous system, it is important to elucidate how the trafficking of these receptors between the cytoplasm and the nucleus and their interactions are regulated by ligand or other molecules to exert transcriptional activity. In this review, the authors focus on the nucleocytoplasmic and subnuclear trafficking of GR and MR in neural cells and nonneural cells and discuss various factors affecting the dynamics of these receptors.