Recycling Ribosomes as a Source of Nutrients – Implications of Neuroplasticity for a Stressed Mind
1 Department of Psychiatry and Psychotherapy, University of Bonn, Venusberg Campus 1, 53127 Bonn, Germany
2 Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstr. 10, 80804 Munich, Germany
Stress is a state of threatened homeostasis stimulated by intrinsic or extrinsic stressors of various nature. Responses to stressors engender a complex bi-directional crosstalk of endocrine, immune, neuronal, and behavioral processes set into motion by the central nervous system-immune-endocrine axis. Acute and chronic stress, and especially the stress-induced release of glucocorticoids, cause changes in neuronal homeostasis that affect functionality of synapses and thereby aspects of cognitive processing. A fundamental molecular mechanism of stress adaptation is the maintenance of proteome balance, regulated by complex proteostasis networks, comprising molecular chaperones and proteolytic machineries, such as autophagy. Control of protein abundance in neurons is achieved across a complex morphology and is tightly linked to synaptic plasticity. Because of their role in local protein synthesis, ribosomes play a key role in establishing and maintaining the synaptic proteome. At the same time, they also act as a nutrient source and, under certain conditions, can be degraded as part of selective autophagy - “ribophagy”. This process may be modulated by the immunophilin FK506-binding protein 51 (FKBP51) - a well-established regulator of endocrine stress responses that has been recently implicated in autophagy. In our work, we will elucidate the function of FKBP51 and identify the molecular mechanisms of the endocrine stress response being responsible for the regulation of ribophagy and how this process underlies neuropsychiatric pathologies.