Stress-primed secretory autophagy promotes extracellular BDNF maturation by enhancing MMP9 secretion

• DOI: 10.1038/s41467-021-24810-5
• Publication Date: 2021-07-30T10:04:43Z
• Authors: Silvia Martinelli; Elmira A. Anderzh...; Thomas Bajaj; Svenja Wiechmann; Frederik Dethloff; Katja Weckmann; Daniel E. Heinz; Tim Ebert; Jakob Hartmann; Thomas M. Geiger; Michael Döngi; Kathrin Hafner; Max L. Pöhlmann; Lee Jollans; Alexandra Philipsen; Susanne V. Schmidt; Ulrike Schmidt; Giuseppina Maccar...; Valentin Stein; Felix Hausch; Christoph W. Turck; Mathias V. Schmidt; Anne-Kathrin Gellner; Bernhard Kuster; Nils C. Gassen
• Keywords: MMP9; Homeostasis

Abstract The stress response is an essential mechanism for maintaining homeostasis, and its disruption implicated in several psychiatric disorders. On the cellular level, activates, among other mechanisms, autophagy that regulates homeostasis through protein degradation recycling. Secretory a recently described pathway which autophagosomes fuse with plasma membrane rather than lysosomes. Here, we demonstrate glucocorticoid-mediated enhances secretory via stress-responsive co-chaperone FK506-binding 51. We identify matrix metalloproteinase 9 (MMP9) as one of proteins secreted to stress. Using assays vivo microdialysis, further find stress-enhanced MMP9 secretion increases cleavage pro-brain-derived neurotrophic factor (proBDNF) mature form (mBDNF). BDNF adult synaptic plasticity associated major depression posttraumatic disorder. These findings unravel adaptation bears potential opening avenues understanding pathophysiology stress-related