SIPA1L2 controls trafficking and local signaling of TrkB-containing amphisomes at presynaptic terminals
| Autor: | Nicola Brice, Michael R. Kreutz, Jeffrey Lopez-Rojas, Christina Spilker, Oliver Stork, Maria Andres-Alonso, Torben J. Hausrat, Michaela Schweizer, Mohamed-Raafet Ammar, Gustavo Acuna Sanhueza, Guilherme M. Gomes, Maximilian Borgmeyer, Ioana Butnaru, Anna Karpova, Silvia Diaz-Gonzalez, Rajeev Raman, PingAn Yuanxiang, Tamar Macharadze, Antonio Virgilio Failla, Mark Carlton, Eckart D. Gundelfinger, Syed Ahsan Raza, Matthias Kneussel |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
General Physics and Astronomy Tropomyosin receptor kinase B Axonal Transport Hippocampus Mice 0302 clinical medicine Axon lcsh:Science Mice Knockout Neurons Multidisciplinary Membrane Glycoproteins Neuronal Plasticity GTPase-Activating Proteins Protein-Tyrosine Kinases Transport protein Cell biology Protein Transport medicine.anatomical_structure Microtubule-Associated Proteins Endosome Science Dynein Presynaptic Terminals Context (language use) Endosomes Biology General Biochemistry Genetics and Molecular Biology Article Synaptic plasticity 03 medical and health sciences medicine Animals Synaptic transmission Organelles Brain-Derived Neurotrophic Factor Autophagy Autophagosomes Dyneins General Chemistry Axons Cellular neuroscience 030104 developmental biology nervous system Neuroscience Axoplasmic transport lcsh:Q 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications Nature Communications, 10(1):5448 Nature Communications, Vol 10, Iss 1, Pp 1-17 (2019) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-019-13224-z |
| Popis: | Amphisomes are organelles of the autophagy pathway that result from the fusion of autophagosomes with late endosomes. While biogenesis of autophagosomes and late endosomes occurs continuously at axon terminals, non-degradative roles of autophagy at boutons are barely described. Here, we show that in neurons BDNF/TrkB traffick in amphisomes that signal locally at presynaptic boutons during retrograde transport to the soma. This is orchestrated by the Rap GTPase-activating (RapGAP) protein SIPA1L2, which connects TrkB amphisomes to a dynein motor. The autophagosomal protein LC3 regulates RapGAP activity of SIPA1L2 and controls retrograde trafficking and local signaling of TrkB. Following induction of presynaptic plasticity, amphisomes dissociate from dynein at boutons enabling local signaling and promoting transmitter release. Accordingly, sipa1l2 knockout mice show impaired BDNF-dependent presynaptic plasticity. Taken together, the data suggest that in hippocampal neurons, TrkB-signaling endosomes are in fact amphisomes that during retrograde transport have local signaling capacity in the context of presynaptic plasticity. There is growing evidence that autophagy might serve specialized functions in neurons besides its role in protein homeostasis. In this study, authors demonstrate that axonal retrograde transport of BDNF/TrkB in neuronal amphisomes is involved in plasticity-relevant local signaling at presynaptic boutons and that SIPA1L2, a member of the SIPA1L family of neuronal RapGAPs, associates via LC3b to TrkB-containing amphisomes to regulate its motility and signaling at the axon terminals |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|