SIPA1L2 controls trafficking and local signaling of TrkB-containing amphisomes at presynaptic terminals
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SIPA1L2 controls trafficking and local signaling of TrkB-containing amphisomes at presynaptic terminals. / Andres-Alonso, Maria; Ammar, Mohamed Raafet; Butnaru, Ioana; Gomes, Guilherme M; Acuña Sanhueza, Gustavo; Raman, Rajeev; Yuanxiang, PingAn; Borgmeyer, Maximilian; Lopez-Rojas, Jeffrey; Raza, Syed Ahsan; Brice, Nicola; Hausrat, Torben J; Macharadze, Tamar; Diaz-Gonzalez, Silvia; Carlton, Mark; Failla, Antonio Virgilio; Stork, Oliver; Schweizer, Michaela; Gundelfinger, Eckart D; Kneussel, Matthias; Spilker, Christina; Karpova, Anna; Kreutz, Michael R.
in: NAT COMMUN, Jahrgang 10, Nr. 1, 29.11.2019, S. 5448.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - SIPA1L2 controls trafficking and local signaling of TrkB-containing amphisomes at presynaptic terminals
AU - Andres-Alonso, Maria
AU - Ammar, Mohamed Raafet
AU - Butnaru, Ioana
AU - Gomes, Guilherme M
AU - Acuña Sanhueza, Gustavo
AU - Raman, Rajeev
AU - Yuanxiang, PingAn
AU - Borgmeyer, Maximilian
AU - Lopez-Rojas, Jeffrey
AU - Raza, Syed Ahsan
AU - Brice, Nicola
AU - Hausrat, Torben J
AU - Macharadze, Tamar
AU - Diaz-Gonzalez, Silvia
AU - Carlton, Mark
AU - Failla, Antonio Virgilio
AU - Stork, Oliver
AU - Schweizer, Michaela
AU - Gundelfinger, Eckart D
AU - Kneussel, Matthias
AU - Spilker, Christina
AU - Karpova, Anna
AU - Kreutz, Michael R
PY - 2019/11/29
Y1 - 2019/11/29
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-019-13224-z
DO - 10.1038/s41467-019-13224-z
M3 - SCORING: Journal article
C2 - 31784514
VL - 10
SP - 5448
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
ER -