The angiotensin type 2 receptor of angiotensin II and neuronal differentiation: from observations to mechanisms

The angiotensin II (Ang II) type 2 receptor (AT(2)) is a member of the seven-transmembrane domain, G-protein coupled receptor family. This receptor is ubiquitously distributed in the fetus but, in most tissues, its expression dramatically falls in the first few hours after birth. Based on this observation, the hypothesis that this receptor could be involved in fetal development was raised and, over the past ten, years, many studies have tried to identify a role for the AT(2) receptor using many different tissues and cell lines. To date, one of the major roles associated with the Ang II AT(2) receptor concerns its ability to induce neuronal differentiation. Indeed, in cells of neuronal origin, activation of the AT(2) receptor was shown to induce neurite outgrowth and elongation, modulate neuronal excitability, promote cellular migration and, in particular conditions, induce neuronal cell death. Regarding its signaling mechanisms, the AT(2) receptor still represents one of the most controversial G-protein coupled receptors since it does not stimulate the production of any of the classical second messengers. This review summarizes knowledge of the functions and the signaling mechanisms involved in the actions of the AT(2) receptor in neurons and cells of neuronal origin. Based on its altered expression in neurological disorders, a role for the AT(2) receptor in control of neuronal plasticity is proposed.