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, Thau-Habermann N, von Collenberg CR, Karl F, Damme M, Horowitz A, et al. (2017)
NATURE COMMUNICATIONS 8: 678.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Lüningschrör, PatrickUniBi; Binotti, Beyenech; Dombert, Benjamin; Heimann, PeterUniBi; Perez-Lara, Angel; Slotta, CarstenUniBi; Thau-Habermann, Nadine; von Collenberg, Cora R.; Karl, Franziska; Damme, Markus; Horowitz, Arie; Maystadt, Isabelle
Alle
Abstract / Bemerkung
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.
Erscheinungsjahr
2017
Zeitschriftentitel
NATURE COMMUNICATIONS
Band
8
Art.-Nr.
678
ISSN
2041-1723
Page URI
https://pub.uni-bielefeld.de/record/2915086

Zitieren

Lüningschrör P, Binotti B, Dombert B, et al. Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease. NATURE COMMUNICATIONS. 2017;8: 678.
Lüningschrör, P., Binotti, B., Dombert, B., Heimann, P., Perez-Lara, A., Slotta, C., Thau-Habermann, N., 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
Lüningschrör, P., Binotti, B., Dombert, B., Heimann, P., Perez-Lara, A., Slotta, C., Thau-Habermann, N., von Collenberg, C. R., Karl, F., Damme, M., et al. (2017). Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease. NATURE COMMUNICATIONS 8:678.
Lüningschrör, P., et al., 2017. Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease. NATURE COMMUNICATIONS, 8: 678.
P. Lüningschrör, et al., “Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease”, NATURE COMMUNICATIONS, vol. 8, 2017, : 678.
Lüningschrör, P., Binotti, B., Dombert, B., Heimann, P., Perez-Lara, A., Slotta, C., Thau-Habermann, N., von Collenberg, C.R., Karl, F., Damme, M., Horowitz, A., Maystadt, I., Fuechtbauer, A., Fuechtbauer, E.-M., Jablonka, S., Blum, R., Ueceyler, N., Petri, S., Kaltschmidt, B., Jahn, R., Kaltschmidt, C., Sendtner, M.: Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease. NATURE COMMUNICATIONS. 8, : 678 (2017).
Lüningschrör, Patrick, Binotti, Beyenech, Dombert, Benjamin, Heimann, Peter, Perez-Lara, Angel, Slotta, Carsten, Thau-Habermann, Nadine, von Collenberg, Cora R., Karl, Franziska, Damme, Markus, Horowitz, Arie, Maystadt, Isabelle, Fuechtbauer, Annette, Fuechtbauer, Ernst-Martin, Jablonka, Sibylle, Blum, Robert, Ueceyler, Nurcan, Petri, Susanne, Kaltschmidt, Barbara, Jahn, Reinhard, Kaltschmidt, Christian, and Sendtner, Michael. “Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease”. NATURE COMMUNICATIONS 8 (2017): 678.

4 Zitationen in Europe PMC

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