CRHR1 endocytosis: Spatiotemporal regulation of receptor signaling

• Published in: Progress in molecular biology and translational science Vol. 196; pp. 229 - 260
• Main Authors: Dos Santos Claro, Paula A, Silbermins, Micaela, Inda, Carolina, Silberstein, Susana
• Format: Journal Article
• Language: English
• Published: Netherlands 2023
• Subjects: Central Nervous System - metabolism; Corticotropin-Releasing Hormone - metabolism; Endocytosis; Humans; Hypothalamo-Hypophyseal System - metabolism; Pituitary-Adrenal System - metabolism; ERK1/2; CRH receptors signaling; CRHR1 sustained signaling; Soluble adenylyl cyclase; cAMP; GPCR endocytosis and signaling
• ISSN: 1878-0814
• DOI: 10.1016/bs.pmbts.2022.07.015

Corticotropin releasing hormone (CRH) is crucial for basal and stress-initiated reactions in the hypothalamic-pituitary-adrenal axis (HPA) and extrahypothalamic brain circuits, where it acts as a neuromodulator to organize behavioral and humoral responses to stress. We review and describe cellular components and molecular mechanisms involved in CRH system signaling through G protein-coupled receptors (GPCRs) CRHR1 and CRHR2, under the current view of GPCR signaling from the plasma membrane but also from intracellular compartments, which establish the bases of signal resolution in space and time. Focus is placed on latest studies of CRHR1 signaling in physiologically significant contexts of the neurohormone function that disclosed new mechanistic features of cAMP production and ERK1/2 activation. We also introduce in a brief overview the pathophysiological function of the CRH system, underlining the need for a complete characterization of CRHRs signaling to design new and specific therapies for stress-related disorders.