CRH signals through a B-Raf-associated complex to induce a biphasic ERK1/2 activation in mouse hippocampal cells

INDA, C.; BONFIGLIO, J.J.; MACCARRONE G.; TURCK, C. W.; HOLSBOER, F.; ARZT, E.; SILBERSTEIN, S.

Buenos Aires

Simposio; Workshop Fronteras en Biociencia, organizado por el Ministerio de Ciencia, Tecnología e Innovación Productiva de la República Argentina y la Sociedad Max Planck.; 2012

, organizado por el Ministerio de Ciencia, Tecnología e Innovación Productiva de la República Argentina y la Sociedad Max Planck

Corticotropin-releasing hormone (CRH) plays a key role in the adjustment of neuro-endocrine, autonomic, and behavioral adap-tations to stress. CRH is the major driver of the hypothalamic-pituitary-adrenal axis, but it is also widely distributed in extrahypo-thalamic circuits where it functions as neuromodulator, coordinating many humoral and behavioral aspects of the stress res-ponse. CRH exerts its actions by two G-protein-coupled receptors, CRH receptor 1 (CRHR1) and CRH receptor 2 (CRHR2), with differential anatomical distribution and ligand affinity. CRH is a high affinity ligand for CRHR1, and the CRH/CRHR1 system dysfunction in limbic structures has been implicated in behavioral alterations, cog-nitive impairments, and emotional respon-ses that are typical of depression and anxiety disorders. The aim of our work is to elucidate mole-cular mechanisms and cellular components involved in CRH signaling which may have implications for the understanding of the physiological function of the hormone in the central nervous system. Given that the signaling pathways triggered by CRH depend on cellular context and that the mechanisms involved in hippocampal neurons are not known, we carried out our studies in the immortalized mouse hippo-campal cell line HT22, stably transfected with murine receptor CRHR1 (HT22-CRHR1).