| Autor: |
Anna Karpova, Tamar Macharadze, Nicola Brice, Antonio Virgilio Failla, Syed Ahsan Raza, Ioana Butnaru, Michael R. Kreutz, Matthias Kneussel, Eckart D. Gundelfinger, Jeffrey Lopez-Rojas, Christina Spilker, Rajeev Raman, Silvia Diaz-Gonzalez, Oliver Stork, PingAn Yuanxiang, Mark Carlton, Michaela Schweizer, Torben J. Hausrat, Guilherme M. Gomes, Maria Andres-Alonso, Mohamed-Raafet Ammar, Gustavo Acuna Sanhueza, Maximilian Borgmeyer |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| DOI: |
10.1101/556266 |
| Popis: |
SummaryAmphisomes are transient organelles that derive from fusion of autophagosomes with late endosomes. They rapidly transform into degradative autolysosomes, whereas non-degradative roles of the autophagic pathway have been barely described. Here we show that in neurons BDNF/TrkB receptor bearing Rab7 / Light chain 3 (LC3) - positive amphisomes signal at presynaptic boutons during retrograde trafficking to the soma. Local signaling and inward transport essentially require the Rap GTPase-activating (RapGAP) protein SIPA1L2, which directly binds to TrkB and Snapin to connect TrkB-containing amphisomes to dynein. Association with LC3 regulates the RapGAP activity of SIPA1L2 and thereby retrograde trafficking. Following induction of presynaptic plasticity amphisomes dissociate from dynein at boutons, and this enables local signaling and promotes transmitter release. Accordingly,sipa1l2knockout mice show impaired BDNF-dependent presynaptic plasticity. Collectively, the data suggest that TrkB-signaling endosomes are in fact amphisomes that during retrograde transport have local signaling capacity in the context of presynaptic plasticity. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
