BDNF signaling requires Matrix Metalloproteinase-9 during structural synaptic plasticity.
| العنوان: | BDNF signaling requires Matrix Metalloproteinase-9 during structural synaptic plasticity. |
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| المؤلفون: | Legutko D; BRAINCITY, Laboratory of Neurobiology, The Nencki Institute, 02-093 Warsaw, Pasteura 3, Poland.; Max Planck Florida Institute for Neuroscience, 1 Max Planck Way, Jupiter, Florida 33458, USA., Kuźniewska B; BRAINCITY, Laboratory of Neurobiology, The Nencki Institute, 02-093 Warsaw, Pasteura 3, Poland.; Current address: Department of Animal Physiology, Institute of Functional Biology and Ecology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096, Warsaw, Poland., Kalita K; BRAINCITY, Laboratory of Neurobiology, The Nencki Institute, 02-093 Warsaw, Pasteura 3, Poland., Yasuda R; Max Planck Florida Institute for Neuroscience, 1 Max Planck Way, Jupiter, Florida 33458, USA., Kaczmarek L; BRAINCITY, Laboratory of Neurobiology, The Nencki Institute, 02-093 Warsaw, Pasteura 3, Poland., Michaluk P; BRAINCITY, Laboratory of Neurobiology, The Nencki Institute, 02-093 Warsaw, Pasteura 3, Poland. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Jan 30. Date of Electronic Publication: 2024 Jan 30. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Synaptic plasticity underlies learning and memory processes as well as contributes, in its aberrant form, to neuropsychiatric disorders. One of its major forms is structural long-term potentiation (sLTP), an activity-dependent growth of dendritic spines that harbor excitatory synapses. The process depends on the release of brain-derived neurotrophic factor (BDNF), and activation of its receptor, TrkB. Matrix metalloproteinase-9 (MMP-9), an extracellular protease is essential for many forms of neuronal plasticity engaged in physiological as well as pathological processes. Here, we utilized two-photon microscopy and two-photon glutamate uncaging to demonstrate that MMP-9 activity is essential for sLTP and is rapidly (~seconds) released from dendritic spines in response to synaptic stimulation. Moreover, we show that either chemical or genetic inhibition of MMP-9 impairs TrkB activation, as measured by fluorescence lifetime imaging microscopy of FRET sensor. Furthermore, we provide evidence for a cell-free cleavage of proBDNF into mature BDNF by MMP-9. Our findings point to the autocrine mechanism of action of MMP-9 through BDNF maturation and TrkB activation during sLTP. Competing Interests: Disclosure and competing interest statement R.Y. is a founder of Florida Lifetime Imaging LLC. |
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| معلومات مُعتمدة: | R01 MH080047 United States MH NIMH NIH HHS; R35 NS116804 United States NS NINDS NIH HHS |
| فهرسة مساهمة: | Keywords: BDNF; Exocytosis; FRET; MMP-9; Synaptic plasticity; dendritic spine; pHluorin; proteolysis |
| تواريخ الأحداث: | Date Created: 20231218 Latest Revision: 20240210 |
| رمز التحديث: | 20240210 |
| مُعرف محوري في PubMed: | PMC10723398 |
| DOI: | 10.1101/2023.12.08.569797 |
| PMID: | 38106209 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2023.12.08.569797 |
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