Martinelli, Silvia ; Anderzhanova, Elmira A. ; Bajaj, Thomas ; Wiechmann, Svenja ; Dethloff, Frederik ; Weckmann, Katja ; Heinz, Daniel E. ; Ebert, Tim ; Hartmann, Jakob ; Geiger, Thomas M. ; Döngi, Michael ; Hafner, Kathrin ; Pöhlmann, Max L. ; Jollans, Lee ; Philipsen, Alexandra ; Schmidt, Susanne V. ; Schmidt, Ulrike ; Maccarrone, Giuseppina ; Stein, Valentin ; Hausch, Felix ; Turck, Christoph W. ; Schmidt, Mathias V. ; Gellner, Anne-Kathrin ; Kuster, Bernhard ; Gassen, Nils C. (2024)
Stress-primed secretory autophagy promotes extracellular BDNF maturation by enhancing MMP9 secretion.
In: Nature Communications, 2021, 12 (1)
doi: 10.26083/tuprints-00023586
Artikel, Zweitveröffentlichung, Verlagsversion
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Kurzbeschreibung (Abstract)
The stress response is an essential mechanism for maintaining homeostasis, and its disruption is implicated in several psychiatric disorders. On the cellular level, stress activates, among other mechanisms, autophagy that regulates homeostasis through protein degradation and recycling. Secretory autophagy is a recently described pathway in which autophagosomes fuse with the plasma membrane rather than with lysosomes. Here, we demonstrate that glucocorticoid-mediated stress enhances secretory autophagy via the stress-responsive co-chaperone FK506-binding protein 51. We identify the matrix metalloproteinase 9 (MMP9) as one of the proteins secreted in response to stress. Using cellular assays and in vivo microdialysis, we further find that stress-enhanced MMP9 secretion increases the cleavage of pro-brain-derived neurotrophic factor (proBDNF) to its mature form (mBDNF). BDNF is essential for adult synaptic plasticity and its pathway is associated with major depression and posttraumatic stress disorder. These findings unravel a cellular stress adaptation mechanism that bears the potential of opening avenues for the understanding of the pathophysiology of stress-related disorders.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2024 |
| Autor(en): | Martinelli, Silvia ; Anderzhanova, Elmira A. ; Bajaj, Thomas ; Wiechmann, Svenja ; Dethloff, Frederik ; Weckmann, Katja ; Heinz, Daniel E. ; Ebert, Tim ; Hartmann, Jakob ; Geiger, Thomas M. ; Döngi, Michael ; Hafner, Kathrin ; Pöhlmann, Max L. ; Jollans, Lee ; Philipsen, Alexandra ; Schmidt, Susanne V. ; Schmidt, Ulrike ; Maccarrone, Giuseppina ; Stein, Valentin ; Hausch, Felix ; Turck, Christoph W. ; Schmidt, Mathias V. ; Gellner, Anne-Kathrin ; Kuster, Bernhard ; Gassen, Nils C. |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | Stress-primed secretory autophagy promotes extracellular BDNF maturation by enhancing MMP9 secretion |
| Sprache: | Englisch |
| Publikationsjahr: | 24 September 2024 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 31 Juli 2021 |
| Ort der Erstveröffentlichung: | London |
| Verlag: | Springer Nature |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Nature Communications |
| Jahrgang/Volume einer Zeitschrift: | 12 |
| (Heft-)Nummer: | 1 |
| Kollation: | 17 Seiten |
| DOI: | 10.26083/tuprints-00023586 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/23586 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| Kurzbeschreibung (Abstract): | The stress response is an essential mechanism for maintaining homeostasis, and its disruption is implicated in several psychiatric disorders. On the cellular level, stress activates, among other mechanisms, autophagy that regulates homeostasis through protein degradation and recycling. Secretory autophagy is a recently described pathway in which autophagosomes fuse with the plasma membrane rather than with lysosomes. Here, we demonstrate that glucocorticoid-mediated stress enhances secretory autophagy via the stress-responsive co-chaperone FK506-binding protein 51. We identify the matrix metalloproteinase 9 (MMP9) as one of the proteins secreted in response to stress. Using cellular assays and in vivo microdialysis, we further find that stress-enhanced MMP9 secretion increases the cleavage of pro-brain-derived neurotrophic factor (proBDNF) to its mature form (mBDNF). BDNF is essential for adult synaptic plasticity and its pathway is associated with major depression and posttraumatic stress disorder. These findings unravel a cellular stress adaptation mechanism that bears the potential of opening avenues for the understanding of the pathophysiology of stress-related disorders. |
| Freie Schlagworte: | Autophagy, Cell signalling, Stress and resilience, Synaptic plasticity |
| ID-Nummer: | Artikel-ID: 4643 |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-235864 |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 540 Chemie |
| Fachbereich(e)/-gebiet(e): | 07 Fachbereich Chemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut |
| Hinterlegungsdatum: | 24 Sep 2024 11:10 |
| Letzte Änderung: | 25 Sep 2024 09:01 |
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| Suche nach Titel in: | TUfind oder in Google |
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- Stress-primed secretory autophagy promotes extracellular BDNF maturation by enhancing MMP9 secretion. (deposited 24 Sep 2024 11:10) [Gegenwärtig angezeigt]
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