FK506-BINDING PROTEIN 51 (FKBP51) EXPRESSION IS MODULATED UPON SERUM DEPRIVATION AND MAY PLAY A ROLE IN THE REGULATION OF THE AUTOPHAGY PATHWAY IN THE HYPOTHALAMIC CONTEXT

BELÉN UGO; SENIN, SERGIO; LIBERMAN, ANA CLARA; ROMINA GOBBINI; BUDZIÑSKI, MAIA LUDMILA; ARZT, EDUARDO; CLARA SOKN; MARIANA ERDOCIA

Congreso; LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2020

Sociedad Argentina de Investigación Clínica

FK506-binding protein 51 (FKBP51) is an Hsp90 co-chaperone that has been described to regulate the activity of the glucocorticoid receptor (GR) and is therefore critical for the regulation of the stress response. In order to act as a GR regulator, our group has demonstrated that FKBP51 has to be SUMOylated, a process enhanced by cellular stress. FKBP51 also acts as a metabolic sensor playing an important role in energy and metabolic homeostasis. At the brain level, the hypothalamus has a central role in the control of body homeostasis, neuroendocrine outputs, and feeding behaviour. It does so by sensing and integrating signals from the periphery and effecting appropriate physiological changes. Hypothalamic FKBP51 is induced by fasting, and elevated hypothalamic expression promotes obese phenotypes. Interestingly, several studies have described a role for hypothalamic autophagy in the control of food intake and energy balance. At the molecular level, FKBP51 has been shown to bind Beclin1 and alter its phosphorylation status, promoting the induction of the autophagy pathway. It does so by interacting with PHLPP and AKT1 and thereby favouring AKT?s dephosphorylation, which leads to Beclin1 recruitment and dephosphorylation. Furthermore, synthetic glucocorticoids and antidepressants act synergistically with FKBP51 in the induction of autophagy. Our preliminary western blot results show that FKBP51 expression is up-regulated upon starvation in the GT1-7 hypothalamic cell line (35.5±3.3%, p