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  Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease.

Lüningschrör, P., Binotti, B., Dombert, B., Heimann, P., Perez-Lara, A., Slotta, C., et al. (2017). Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease. Nature Communications, 8: 678. doi:10.1038/s41467-017-00689-z.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-1DF9-E Version Permalink: http://hdl.handle.net/21.11116/0000-0001-30CE-1
Genre: Journal Article

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 Creators:
Lüningschrör, P., Author
Binotti, B.1, Author              
Dombert, B., Author
Heimann, P., Author
Perez-Lara, A.1, Author              
Slotta, C., Author
Thau-Habermann, N., Author
von Collenberg, C. R., Author
Karl, F., Author
Damme, M., Author
Horowitz, A., Author
Maystadt, I., Author
Füchtbauer, A., Author
Füchtbauer, E. M., Author
Jablonka, S., Author
Blum, R., Author
Üçeyler, N., Author
Petri, S., Author
Kaltschmidt, B., Author
Jahn, R.1, Author              
Kaltschmidt, C., AuthorSendtner, M., Author more..
Affiliations:
1Department of Neurobiology, MPI for Biophysical Chemistry, Max Planck Society, ou_578595              

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 Abstract: Autophagy-mediated degradation of synaptic components maintains synaptic homeostasis but also constitutes a mechanism of neurodegeneration. It is unclear how autophagy of synaptic vesicles and components of presynaptic active zones is regulated. Here, we show that Pleckstrin homology containing family member 5 (Plekhg5) modulates autophagy of synaptic vesicles in axon terminals of motoneurons via its function as a guanine exchange factor for Rab26, a small GTPase that specifically directs synaptic vesicles to preautophagosomal structures. Plekhg5 gene inactivation in mice results in a late-onset motoneuron disease, characterized by degeneration of axon terminals. Plekhg5-depleted cultured motoneurons show defective axon growth and impaired autophagy of synaptic vesicles, which can be rescued by constitutively active Rab26. These findings define a mechanism for regulating autophagy in neurons that specifically targets synaptic vesicles. Disruption of this mechanism may contribute to the pathophysiology of several forms of motoneuron disease.

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Language(s): eng - English
 Dates: 2017-10-30
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1038/s41467-017-00689-z
 Degree: -

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Title: Nature Communications
Source Genre: Journal
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Pages: 17 Volume / Issue: 8 Sequence Number: 678 Start / End Page: - Identifier: -