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

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

Congreso; LXV Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2020

Sociedad Argentina de Investigación Clínica (SAIC)

FK506-binding protein 51 (FKBP51) is an Hsp90 co-chaperone that has been described toregulate the activity of the glucocorticoid receptor (GR) and is therefore critical for the regulation ofthe stress response. In order to act as a GR regulator, our group has demonstrated that FKBP51has to be SUMOylated, a process enhanced by cellular stress. FKBP51 also acts as a metabolicsensor playing an important role in energy and metabolic homeostasis. At the brain level, thehypothalamus has a central role in the control of body homeostasis, neuroendocrine outputs, andfeeding behaviour. It does so by sensing and integrating signals from the periphery and effectingappropriate physiological changes. Hypothalamic FKBP51 is induced by fasting, and elevatedhypothalamic expression promotes obese phenotypes. Interestingly, several studies havedescribed a role for hypothalamic autophagy in the control of food intake and energy balance. Atthe 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 AKT1and thereby favouring AKT?s dephosphorylation, which leads to Beclin1 recruitment anddephosphorylation. Furthermore, synthetic glucocorticoids and antidepressants act synergisticallywith FKBP51 in the induction of autophagy. Our preliminary western blot results show thatFKBP51 expression is up-regulated upon starvation in the GT1-7 hypothalamic cell line(35.5±3.3%, p